
I Le contrat de vente classique 1. LâintĂ©rĂȘt pour la PMI de connaĂźtre la diversitĂ© des contrats commerciaux Les PME-PMI sont rĂ©guliĂšrement amenĂ©es Ă conclure des contrats commerciaux. Il est donc nĂ©cessaire pour lâassistant(e) de gestion de connaĂźtre les diffĂ©rents contrats et les rĂšgles qui les rĂ©gissent. 2. Le transfert de propriĂ©tĂ© DĂšs quâil y a accord entre le vendeur et lâacheteur, il y a transfert de propriĂ©tĂ©. Lâacheteur doit donc assumer les risques dĂšs le transfert de propriĂ©tĂ©. Pour pallier ce risque, il peut prĂ©voir dans le contrat une clause de rĂ©serve en propriĂ©tĂ©, qui a pour effet de diffĂ©rer le transfert de la propriĂ©tĂ© et des risques quâil entraine jusqu'Ă conclusion totale du contrat. 3. Les obligations des parties Les garanties dans le contrat de vente se dĂ©composent ainsi : ï Les garanties obligatoires : o la garantie lĂ©gale de conformitĂ© permettant au client dâobtenir la rĂ©paration, le remboursement ou le remplacement du produit dĂ©fectueux o la garantie contre les vices cachĂ©s : se sont des dĂ©fauts non visibles au moment de lâachat qui rendent le bien inutilisable ï Les garanties complĂ©mentaires ou commerciales : elles sont facultatives pour le client. Elles peuvent ĂȘtre gratuites (mise Ă disposition dâun produit au client durant une rĂ©paration) ou payantes (extension de garantie pour lâachat dâune machine Ă laver) Exercice dâapplication 4. Les recours possibles Lorsquâune procĂ©dure est engagĂ©e, la juridiction compĂ©tente pour statuer lâaffaire est le tribunal de commerce du dĂ©fendeur si le client et lâentreprise sont des commerçants. Les sanctions les plus courantes sont : - infliger des pĂ©nalitĂ©s de retard - obtenir une rĂ©duction de prix - faire exĂ©cuter le contrat par une autre entreprise - obtenir des dommages et intĂ©rĂȘts II Les particularitĂ©s du contrat de vente commerciale Le contrat prĂ©sente certaines particularitĂ©s que la PME doit connaitre : On peut donc considĂ©rer quâun bon de commande est un contrat de vente commerciale, dans la mesure oĂč il rĂ©unit ses clauses. Enfin, il existe des situations ou les engagements peuvent diffĂ©rĂ©s. Câest le cas : - de la vente Ă distance : le client dispose dâun dĂ©lai de rĂ©tractation de 14 jours - la vente avec arrhes : si le client verse des arrhes, il pourra annuler le contrat mais perdra le montant versĂ© Ă lâentreprise. III Les contrats de maintenance et de sous6traitance 1. Le contrat de maintenance Câest un contrat par lequel une entreprise se charge de vĂ©rifier, dâentretenir ou de rĂ©parer un appareil technique ou une installation complexe. Il doit donc spĂ©cifier : - la dĂ©finition de la prestation et le lieu de rĂ©alisation - la durĂ©e du contrat - le prix unitaire ou forfaitaire 2. Le contrat de sous-traitance Il permet Ă une entreprise appelĂ©e « donneur dâordre » de confier la rĂ©alisation dâune prestation Ă une autre entreprise appelĂ©e « sous traitant ». Lâentreprise sâengage Ă payer le sous traitant selon les modalitĂ©s prĂ©vues dans le contrat et reste donc responsable de la rĂ©alisation de la prestation devant le client. Avantages et inconvĂ©nients de la sous-traitance : IV CrĂ©er un contrat via un rĂ©seau de franchise Afin de dĂ©velopper son activitĂ©, lâassistant(e) de gestion peut conclure des contrats commerciaux avec des partenaires Ă©trangers La franchise est une mĂ©thode de collaboration entre, dâune part, une entreprise, le franchiseur, et, dâautre part, une ou plusieurs entreprises, les franchisĂ©s. Son objet est dâexploiter un concept de franchise mis au point par le franchiseur. Tous sont porteurs de la mĂȘme enseigne, symbole de lâidentitĂ© et de la rĂ©putation du rĂ©seau. La garantie de qualitĂ© est assurĂ©e par la transmission et le contrĂŽle du respect du savoir-faire et par la mise Ă disposition dâune gamme homogĂšne de produits, de services et/ou de technologies. a. Le franchiseur Câest un entrepreneur indĂ©pendant qui a mis au point et exploitĂ© avec succĂšs un concept original dans plusieurs unitĂ©s pilotes. Il apporte Ă ses franchisĂ©s une formation initiale et permanente pour leur permettre dâappliquer son concept et consacre Ă la promotion de sa marque, Ă la recherche et Ă lâinnovation, les moyens humains et financiers permettant dâassurer le dĂ©veloppement et la pĂ©rennitĂ© de son concept. b. Le franchisĂ© Câest un entrepreneur indĂ©pendant sĂ©lectionnĂ© par le franchiseur. Il doit avoir la volontĂ© de collaborer loyalement Ă la rĂ©ussite du rĂ©seau de franchise en adhĂ©rant au principe dâhomogĂ©nĂ©itĂ© de ce rĂ©seau, tel que dĂ©fini par le franchiseur. Il engage des moyens financiers, afin de rĂ©tribuer le franchiseur pour ses apports (paiement dâun droit dâentrĂ©e et dâun pourcentage sur le chiffre dâaffaires). c. Les avantages et les inconvĂ©nients du contrat de franchise pour le franchiseur et pour le franchisĂ©. Avantages InconvĂ©nients Franchiseur â DĂ©velopper son rĂ©seau Ă moindres frais. â Faire des Ă©conomies dâĂ©chelle. â MaĂźtriser le dĂ©veloppement de son concept. â DĂ©velopper son image, sa notoriĂ©tĂ©. â Augmenter ses parts de marchĂ©. â AccroĂźtre son chiffre dâaffaires. â Organiser des campagnes publicitaires Ă lâĂ©chelon national. â Transmettre son savoir-faire Ă des commerçants indĂ©pendants. â Assurer une assistance technique et des formations. â Avoir des franchisĂ©s qui dĂ©prĂ©cient lâimage de lâentreprise. FranchisĂ© â Avoir une notoriĂ©tĂ© dĂšs lâouverture du commerce. â Rester un commerçant indĂ©pendant et ĂȘtre responsable de son entreprise. â BĂ©nĂ©ficier du savoir-faire du franchiseur. â BĂ©nĂ©ficier dâune assistance technique, de formations, dâune logistique dâapprovisionnements, etc. â Respecter la charte et les normes du franchiseur, ce qui limite sa libertĂ© de commerçant indĂ©pendant. â Sâacquitter des droits dâentrĂ©e et de redevance. â Avoir une obligation dâapprovisionnement exclusif chez le franchiseur. d. Les clĂ©s de la rĂ©ussite de cette forme de commerce Les clĂ©s de la rĂ©ussite sont : â la collaboration commerciale et technique ; â lâassociation du savoir-faire du franchiseur et de lâesprit entrepreneurial du franchisĂ© ; â les structures organisationnelles sont plus simples et plus Ă©conomiques quâen succursalisme car un bon franchisĂ© est motivĂ© et nâa pas besoin dâĂȘtre poussĂ© ; â câest un systĂšme rapide et Ă©volutif pour couvrir un marchĂ© car investissements et compĂ©tences sont partagĂ©es. e. Les chiffres clĂ©s de la franchise en 2019 f. La typologie des franchisĂ©s âą 60% des franchisĂ©s sont des hommes âą 50% des franchisĂ©s ont entre 35 et 49 ans âą 66% des franchisĂ©s sont dâanciens salariĂ©s du privĂ© âą Chaque franchisĂ© emploie en moyenne 7 salariĂ©s âą 84% des rĂ©seaux sont toujours la propriĂ©tĂ© de leur fondateur âą Chaque rĂ©seau crĂ©e en moyenne 8 nouveaux points de vente par an âą 29% des rĂ©seaux ont des points de vente Ă lâĂ©tranger
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I Suivre les ventes et les livraisons La plupart du temps, les commandes des clients vont dĂ©clencher les rĂšglements. RĂ©ceptionner les commandes et les traiter rigoureusement est donc une activitĂ© essentielle pour la PME. 1. La rĂ©ception de la commande Avant de traiter la commande, il est important quâelle soit vĂ©rifiĂ©e pour optimiser la relation client et Ă©viter les erreurs. Les points de contrĂŽle sont : 2. Le traitement de la commande Les documents Ă gĂ©nĂ©rer sur le PGI sont : 3. Le suivi de la commande Le suivi permet Ă lâentreprise de surveiller la progression de lâensemble des commandes. Lâentreprise peut ainsi crĂ©er un tableau de suivi visuel lui permettant dâanticiper les problĂšmes de livraison. Voici un exemple : 4. Lâorganisation et le suivi des livraisons Livrer, câest mettre Ă la disposition du client les produits commandĂ©s Ă la date prĂ©vue et au lieu convenu. Lâentreprise peut dĂ©cider de livrer elle-mĂȘme out de faire appel Ă un transporteur : âą La prise en charge de la livraison par le fournisseur La PME organise le planning et la tournĂ©e des livreurs en tenant compte des attentes du client, du temps de trajet et du volume Ă livrer. Elle utilise pour chaque Ă©tape le bon de livraison. Un exemplaire est conservĂ© par lâentreprise et un exemplaire sera laissĂ© au client lors de la livraison. âą La prise en charge de la livraison via un transporteur Le suivi de la livraison : Le contrat gĂ©nĂ©ral de vente permet dâanticiper les problĂšmes et de limiter les contestations (retards de livraison). Les frais de transport doivent donc figurer sur le bon de livraison. Trois type de frais existent : âȘ franco de port : âȘ port dĂ» : Certains transporteurs offrent la possibilitĂ© de suivre les expĂ©ditions sur leur site Web. II Facturer, suivre les rĂšglements et les relances clients 1. La facture A chaque Ă©tape du processus de vente, divers documents sont créés. Le dernier document du processus est la facture. Elle indique le paiement Ă faire au client et prouve la vente : facture de doit. Chaque facture portant une date et un numĂ©ro unique, une fois Ă©mise, il nâest donc plus possible de lâannuler ou la modifier .Sâil se passe un Ă©vĂšnement aprĂšs lâĂ©dition, on devra alors Ă©mettre un avoir. Le processus peut se schĂ©matiser ainsi : 2. La prĂ©sentation dâune facture La facture est Ă©tablit en double exemplaire et doit ĂȘtre conservĂ©e pendant 10 ans. Elle rĂ©sulte dâune obligation lĂ©gale et se matĂ©rialise par un enregistrement comptable. Quelques rĂšgles sont Ă respecter : 3. Les Ă©lĂ©ments Ă contrĂŽler sur la facture Il est nĂ©cessaire de vĂ©rifier les mentions obligatoires afin dâĂ©viter les rĂ©clamations clients. Si elle est conforme, elle est envoyĂ©e au client et transmise au service comptabilitĂ© pour lâenregistrement. Les Ă©lĂ©ments Ă vĂ©rifier sont : 4. Les aspects fiscaux liĂ©s aux ventes : le mĂ©canisme de TVA Lâenregistrement des ventes doit se faire dans le respect des rĂšgles fiscales relatives Ă la TVA (taxe sur la valeur ajoutĂ©e) Il existe 4 taux principaux de TVA en France : Certaines activitĂ©s et certains territoires sont exonĂ©rĂ©s de TVA. âą Le taux de TVA intermĂ©diaire de 10 % sâapplique pour les activitĂ©s suivantes : Restauration (pour consommation immĂ©diate) Aide Ă la personne HĂ©bergement et transport Produits agricoles non transformĂ©s et bois de chauffage MĂ©dicaments non remboursĂ©s Travaux et rĂ©paration pour les logements anciens (plus de deux ans) MusĂ©es et zoos âą Le taux de TVA rĂ©duit Ă 5.5 % sâapplique pour les activitĂ©s et produits suivants : Produits alimentaires de premiĂšre nĂ©cessitĂ© Fourniture de chaleur produite Ă partir dâĂ©nergies renouvelables Livres (y compris numĂ©riques) Billetterie de spectacle vivant Restauration pour les cantines scolaire Ăquipements pour personnes handicapĂ©es Travaux dâamĂ©lioration Ă©nergĂ©tique des logements de plus de 2 ans âą Le taux de TVA spĂ©cifique Ă 2,1% sâapplique pour les activitĂ©s suivantes : MĂ©dicaments remboursĂ©s par la SĂ©curitĂ© sociale Publications de presse Billetterie de certains spectacles et cinĂ©mas Animaux vivants de boucherie et de charcuterie vendus Ă des non-assujettis âą Les activitĂ©s suivantes sont exonĂ©rĂ©es de TVA (0%) : PĂȘche en mer Certaines Ćuvres non lucratives Ă caractĂšre social ou philanthropique ActivitĂ©s mĂ©dicales et paramĂ©dicales Enseignement et formation Livraison ou rĂ©cupĂ©ration de dĂ©chets Le principe de la TVA pour les entreprises : Afin de bien rĂ©aliser les Ă©critures comptables, il est important de diffĂ©rencier la TVA dĂ©ductible de la TVA collectĂ©e : Une crĂ©ance client est enregistrĂ©e en dĂ©bit alors que la vente de marchandises de lâentreprise est enregistrĂ©e en crĂ©dit. 5. Les Ă©critures comptables relatives aux ventes Les diffĂ©rents Ă©lĂ©ments dâune facture doivent ĂȘtre enregistrĂ©s dans le journal et dans les comptes de lâentreprise. Si lâentreprise dispose dâun PGI, le devis gĂ©nĂšre automatiquement la commande. La commande gĂ©nĂšre automatiquement le bon de livraison qui gĂ©nĂšre la facture. La facture gĂ©nĂšre automatiquement les Ă©critures comptables au journal. Exemple de visualisation dâĂ©criture comptable sur le PGI : 6. La mise en place dâun suivi efficace des rĂšglements Le suivi des comptes clients permet de connaitre lâĂ©tat des crĂ©ances Ă tout moment. La relance remplit plusieurs objectifs : Les outils les plus utilisĂ©s dans cette dĂ©marche sont lâĂ©chĂ©ancier (il liste les crĂ©ances en attente de rĂšglement avec peu de dĂ©tails) et la balance ĂągĂ©e (elle prĂ©sente les soldes de crĂ©ances de maniĂšre plus visuelle avec une ligne par client). Exemples : EchĂ©ancier Balance ĂągĂ©e Lâentreprise peut Ă©galement pointer les crĂ©ances afin de faire ressortir les crĂ©ances impayĂ©es (lettrage des comptes). Enfin, compte tenu des enjeux pour les entreprises dâobtenir les rĂšglements dans des dĂ©lais raisonnables, elles mettent en place un vĂ©ritable processus de relance qui doit respecter les Ă©tapes suivantes : AprĂšs avoir pris connaissance du processus de relance, il devient nĂ©cessaire de crĂ©er un tableau de relance des impayĂ©s pour relancer les clients efficacement. Exemple : Tableau de relances des impayĂ©s : Enfin, il faudra relancer les clients par tĂ©lĂ©phone, mail ou courrier pour obtenir les sommes dues via des relances automatisĂ©es. Exemple de mise en demeure automatisĂ©e envoyĂ©e en recommandĂ© :
Figlio di un decurione, Patricio, ancora pagano, e della cristiana Monnica, fu iscritto tra i catecumeni; compĂŹ gli studi in patria, a Madaura, poi a Cartagine: periodo da lui descritto come di abbandono alle passioni amorose. Da una concubina ebbe nel 372 un figlio, Adeodato. La lettura dell'Hortensius ciceroniano lo attrasse, diciannovenne, alla filosofia, e aderĂŹ presto al manicheismo, presentatogli come spiegazione scientifica dell'universo. Se ne fece anzi propagandista a Tagaste, dopo la morte del padre, e a Cartagine ove ottenne qualche successo come retore, e scrisse il suo primo libro, De pulchro et apto (perduto), in cui pare si sforzasse a dare veste filosofica al manicheismo, nel quale era perĂČ rimasto semplice uditore. PassĂČ poi, abbandonando la madre, a Roma; quindi, su raccomandazione di Simmaco, come professore ufficiale di retorica (autunno 384), a Milano, ove maturĂČ la crisi spirituale, in seguito alla quale, dimessa la concubina e rinunciando al matrimonio vantaggioso per cui insisteva Monnica, si decise ad abbracciare il cristianesimo, che gli si palesava, allora, come in pieno e perfetto accordo con la filosofia neoplatonica e la predicazione di s. Ambrogio. A Cassiciacum (probabilmente Cassago, in Brianza), dimessosi dalla cattedra, scrisse le prime opere pervenuteci (i dialoghi Contra academicos, De vita beata, De ordine e Soliloquia) e cominciĂČ a comporre una serie di manuali delle arti liberali; fu battezzato da s. Ambrogio la notte del sabato santo (24-25 aprile) del 387. Trascorse a Roma l'inverno (Monnica morĂŹ ad Ostia nel novembre) e tornĂČ a Tagaste, continuando, nella vita monastica, la sua attivitĂ di scrittore. Nel 391 fu ordinato sacerdote a Ippona, ove, tra la fine del 395 e il 396, fu consacrato come successore dal vescovo Valerio giĂ prossimo a morte; lo stesso fece poi (426) A. col prete Eraclio. Le reliquie, portate in Sardegna da s. Fulgenzio e altri vescovi esuli nel 486, furono dopo l'invasione saracena trasportate, per opera del re Liutprando, a Pavia ove gli fu eretto il monumento: ma che fossero di lui quelle ritrovate nel 1695 fu contrastato dal Muratori e da altri. Nei 34 anni di episcopato lo tennero occupato, oltre le cure costanti dedicate alla sua chiesa, la copiosa corrispondenza (ci sono giunte 218 lettere di A., oltre i trattatelli in forma epistolare, e 53 dirette a lui), la predicazione (i sermoni conservati e noti finora sono piĂč di 500), i concilĂź e le eresie e scismi, la lotta contro i quali assorbĂŹ grandissima parte dell'attivitĂ letteraria, che ha reso A. proverbiale come uno non solo dei piĂč dotti e profondi, ma dei piĂč fecondi scrittori mai esistiti. Appunto le polemiche, insieme con la conversione, l'ordinazione e la consacrazione, contrassegnano, all'ingrosso, anche periodi dello svolgimento del pensiero di lui. Con la conversione comincia la polemica contro i manichei, giĂ accennata nei "Dialoghi di Cassiciaco" e continuata in una serie di scritti per lo piĂč filosofico-religiosi (per es. De quantitate animae, De libero arbitrio, il libro VI De musica, De magistro, De vera religione, De utilitate credendi), in cui vediamo A. passare gradatamente dall'affermazione della superioritĂ essenziale della ragione sulla fede, a quella dell'utilitĂ e ragionevolezza dell'affidarsi all'auctoritas fondata sulla rivelazione e universalmente riconosciuta, della Chiesa; ed elaborare insieme la sua caratteristica dottrina della conoscenza. La felicitĂ , cui gli uomini aspirano, non si consegue senza il possesso della veritĂ . Contro gli scettici, egli usa l'argomento principe: se dubito, so di dubitare, dunque di essere; se sbaglio, sono (motivo che da taluni storici della filosofia viene indicato tra gli antecedenti del dubbio cartesiano: non sfugge comunque il diverso contesto). Ma la veritĂ va cercata in me stesso: Ăš la dottrina neoplatonica del ritorno su sĂ© stessa dell'anima, che, riconosciuta la mutevolezza del mondo esteriore, percepito dai sensi, e la sua propria, si avvia a ricercare la veritĂ immutabile, per cui Ăš vero ogni ragionamento vero, e che Ăš Dio medesimo. I sensi, dunque, e anche le parole del maestro, non fanno se non ridestare idee, che sono giĂ nell'anima: non perĂČ nel senso della dottrina platonica della reminiscenza, ma in quanto in interiore homine habitat veritas, parla cioĂš, in fondo all'anima, il Maestro interiore, il Verbo divino; nell'uomo (in interiore homine) brilla la luce del vero che dona a ciascuno le rationes aeternae, principio e fondamento di ogni giudizio. Ă questa la teoria detta dell'illuminazione, che, non del tutto chiarita da A., si presta a varie interpretazioni (secondo che le rationes aeternae si intendano come "idee innate", o come "categorie" del giudizio); essa si collega alla dottrina del "maestro interiore", il Verbo, il solo vero maestro: sicchĂ© l'insegnare degli uomini Ăš solo un preparare ad ascoltare la voce del Verbo divino. Queste dottrine furono da A. mantenute anche in opere posteriori ma il primitivo entusiasmo per Platone, Plotino e i "platonici" (che, se fossero vissuti ora, - dice - si sarebbero fatti cristiani) e per i neoplatonici si affievolĂŹ col tempo. La polemica antimanichea venne continuata in altri scritti (per es. Contra Adimantum, Contra epistolam Manichaei quam vocant fundamenti) fino al voluminoso Contra Faustum e ad altri opuscoli fino al 405 circa, poi sporadicamente in un paio di opuscoli e, in parte, nel trattatello contro tutte le eresie (De haeresibus, 428-29). L'ordinazione sacerdotale obbliga A. a spiegare al popolo i libri sacri; egli partecipa piĂč intimamente della vita della Chiesa e viene a conoscere lo scisma che tormenta la Chiesa africana. Comincia cosĂŹ la polemica contro il donatismo, con l'interessante Psalmus abecedarius contra partem Donati, primo esempio degli scritti popolareggianti di A. (versi di 16 sillabe, abbandono della prosodia e metrica classica, assonanza in e), poi con una serie di opere (Contra epistolam Parmeniani, De baptismo, Contra litteras Petiliani, Contra Cresconium) fino alla grande "conferenza" di Cartagine (411; Breviculus collationis cum donatistis) quindi, con minor frequenza di scritti, sino al Contra Gaudentium (420 circa). In questa polemica, che lo portĂČ a occuparsi dell'ecclesiologia, A. segue s. Cipriano e s. Ottato mantenendo fermissimo il principio della validitĂ ed efficacia obiettiva (ex opere operato) dei Sacramenti, la cattolicitĂ e l'unitĂ della Chiesa, fuori della quale non v'Ăš salvezza e che Ăš corpus permixtum: ne fanno parte cioĂš grano e zizzania, buoni e malvagi, che soltanto GesĂč Cristo ha diritto di separare nel giorno del Giudizio. Ma mentre all'inizio, e ancora nel 411, A. non voleva ricorrere ad altro mezzo che la persuasione attraverso la discussione, tuttavia, con le leggi di Onorio contro gli scismatici e di fronte alla loro ostinazione, cambiĂČ parere: e come dalla netta distinzione tra scisma ed eresia passĂČ a definire questa quale "scisma inveterato", cosĂŹ ammise la legittimitĂ e necessitĂ della coercizione e del ricorso all'autoritĂ civile, fissando altresĂŹ il dovere per il sovrano cristiano di attenersi al magistero della chiesa.Ma con l'ordinazione A. si dedica anche con maggiore intensitĂ allo studio della Bibbia: specialmente del Genesi, passando dall'interpretazione strettamente allegorica (De Genesi adversus Manichaeos, 388-90) a quella letterale, e insieme di valore filosofico (De Genesi ad litteram liber imperfectus), e di s. Paolo (Expositio quarundam propositionum ex Epistola ad Romanos, Epistolae ad Romanos expositio inchoata, Expositio Epistolae ad Galatas, parecchie delle questioni trattate nel De diversis quaestionibus octogintatribus). Cogliamo qui un momento importantissimo nello svolgimento del pensiero teologico di A., e oggetto di molte discussioni. Egli si Ăš sforzato di mantenere in primo luogo la giustizia di Dio, che premia i buoni, cioĂš coloro che credendo si acquistano un merito, e che punisce i malvagi. Ma, dopo un lungo sforzo, A. viene a riconoscere che il momento iniziale dell'atto di fede, l'initium fidei, che Ăš initium salutis, non Ăš opera dell'uomo ma viene da Dio: al quale non si puĂČ tuttavia rimproverare alcuna ingiustizia, se, gratuitamente, fa grazia ad alcuni; mentre gli uomini tutti, in cui sopravvive il peccato originale, non meritano se non la condanna. Questi concetti appaiono per la prima volta con tutta chiarezza, nel primo scritto posteriore all'episcopato di A., il De diversis quaestionibus ad Simplicianum. Frutto di questa conquista del suo pensiero, che lo induce a rimeditare sulla sua vita, si possono considerare le Confessioni (398 circa), nelle quali, altresĂŹ, sono ripresi altri due temi che lo appassionano: quello della cultura cristiana e quello dei principĂź che presiedono all'interpretazione della Scrittura. La prima questione Ăš da lui affrontata sotto l'aspetto teorico nel De doctrina christiana (interrotto, ma ripreso e terminato nel 426): come anche nelle Confessioni A. Ăš sensibile ai pericoli della cultura tradizionale, pagana, ma vuole salvarne il buono, che va assunto e fatto proprio dal cristianesimo. CosĂŹ, conchiudendo una lunga controversia, A. assicura col peso della sua autoritĂ la trasmissione della cultura antica. Ma nelle Confessioni il problema della memoria (in essa Ăš la misura del tempo) trascina seco quello della creazione. A. la ritiene avvenuta nel tempo, anzi col tempo, dal nulla, e per tutte le cose simultaneamente, ma non allo stesso modo: chĂ© alcune furono create da Dio non in atto e nella loro forma perfetta, ma solo in potenza, o in germe (rationes seminales, energie latenti destinate a svilupparsi nel tempo e a produrre, al momento opportuno per ciascuno, i diversi esseri). A queste conclusioni A. Ăš portato da un nuovo studio dei primi 3 capitoli del Genesi (De Genesi ad litteram libri XII, tra il 401 circa e il 415 circa). Accanto al quale, tra le opere esegetiche, vanno ricordati il De consensu evangelistarum (400 circa), le Enarrationes in Psalmos, e i Tractatus in evangelium Iohannis, raccolte di sermoni su questi libri. Ma nelle Confessioni A. ha inserito anche un'istruzione catechetica (proprio con il commento al Genesi), affine a quella da lui data in un'altra operetta, il De catechizandis rudibus (400 circa). E il motivo della memoria, che appare nelle Confessioni, diventa importantissimo in un altro trattato su cui A. si affaticĂČ lungo (400 circa -416 circa): il De Trinitate. L'anima Ăš un pensiero (mens) da cui nasce una conoscenza (notitia), e nel suo rapportarsi a questa conoscenza nasce l'amore che essa si porta (amor). Nell'anima o, meglio, nella memoria, nell'intelletto e nella volontĂ , nella parte cioĂš piĂč alta e nobile di essa, che ricorda, comprende e ama sĂ© stessa, ma soprattutto ricorda, conosce e ama Dio, A. scorge le "vestigia" della TrinitĂ divina. Di essa, criticando talvolta le formule di s. Ilario di Poitiers, egli mette in rilievo l'unitĂ di sostanza, insistendo sull'uguaglianza delle tre Persone: le operazioni ad extra sono l'opera indistinta di tutte, ciĂČ che si dice di ciascuna quanto alla sostanza, e anche alla sapienza e altri attributi, Ăš comune, uguale, identico e numericamente uno in tutte; mentre esse si distinguono e si oppongono secondo le loro relazioni reciproche. Teoria che, chiarendo la processione dello Spirito Santo principaliter, sĂŹ, dal Padre, ma anche dal Figlio, divenne importantissima per lo svolgimento della teologia occidentale, cui A. ha legato il carattere "cristocentrico", conforme alla tendenza fondamentale del suo pensiero, aggirantesi intorno alla persona e all'opera del Cristo ed alla redenzione dell'uomo dal peccato, mercĂ© la grazia. Intorno a questi temi scoppiĂČ la polemica con Pelagio, giĂ scandalizzatosi in Roma per l'invocazione delle Confessioni a Dio: da quod iubes et iube quod vis e ora rifugiatosi in Africa con il suo compagno Celestio (che, denunciato da Paolino di Milano, venne condannato nel 411 da un concilio locale, a Cartagine). Si possono distinguere in essa varie fasi: quella iniziale, in cui A. combatte ancora soltanto le dottrine, non gli uomini, che sa molto stimati (De peccatorum meritis et remissione, a Marcellino, il l. III composto dopo che A. ebbe conosciuto il commento di Pelagio a s. Paolo; De spiritu et littera ad Marcellinum e, a complemento, per asserire la necessitĂ delle opere buone accanto alla fede, De fide et operibus; nonchĂ© il De bono viduitatis, dedicato a Giuliana, madre di Demetriade, in occasione della monacazione di questa); quella della polemica diretta, provocata dalle vicende di Pelagio in Oriente fino alla condanna da parte del papa Innocenzo I (con la celebre affermazione che, dopo tanti concilĂź, anche Roma locuta est; causa finita est; utinam aliquando finiatur error) e, dopo il grande concilio di Cartagine (418) da papa Zosimo (De natura et gratia contra Pelagium, De perfectione iustitiae hominis, contro Celestio, De gestis Pelagii, De gratia Christi et peccato originali); quella della lotta contro i pertinaci difensori di Pelagio (De nuptiis et concupiscentia ad Valerium comitem, Contra duas epistolas Pelagianorum, Contra Iulianum, e Contra secundam Iuliani responsionem, il cosiddetto Opus imperfectum, contro lo stesso Giuliano di Eclano, interrotto per la morte di A.), intesa al tempo stesso a chiarire la sua dottrina ai monaci di Adrumeto (De gratia et libero arbitrio, e De correptione et gratia, dedicati all'abate Valentino) e a combattere i "semipelagiani" della Gallia meridionale, insorti contro questi scritti (De praedestinatione sanctorum e De dono perseverantiae). Questa dottrina agostiniana del peccato originale, della grazia e della predestinazione, precisatasi ma anche irrigiditasi e spinta alle estreme conseguenze nell'ardore della polemica, si Ăš prestata a varie e contrastanti interpretazioni. A. prende le mosse dalla condizione di Adamo, creato esente dalla morte (posse non mori, diverso da non posse mori proprio degli esseri spirituali) e dalla concupiscenza, capace quindi di non peccare (il posse non peccare, diverso dal non posse peccare degli eletti), e nella piena libertĂ di optare per il bene conformandosi a una ragione che aveva il perfetto predominio sui sensi, capace altresĂŹ di perseverare nel bene, grazie all'aiuto (adiutorium sine quo non) concessogli da Dio. Avendo Adamo peccato, la sua colpa si trasmise all'intero genere umano, divenuto cosĂŹ massa damnata; peccato di origine, che A. dimostra, fra l'altro, in base all'uso della Chiesa di amministrare agli infanti il battesimo che annulla la concupiscenza in quanto reato, ma la lascia sopravvivere actu, cosĂŹ che l'uomo, pur conservando il libero arbitrio, Ăš privato di quella libertas ... quae in Paradiso fuit (Enchir. 26-27). Per poter resistere cioĂš alla concupiscenza, occorre ora un aiuto divino maggiore di quello dato ad Adamo: la grazia Ăš dunque necessaria per avere la fede, e questa perchĂ© vi sia quell'amore di Dio, in quanto sommo bene, senza di che non esiste nĂ© beatitudine nĂ© vera moralitĂ (e non vi sono pertanto vere virtĂč fra i pagani). Ma questo soccorso (adiutorium quo) non Ăš concesso a tutti: Dio, senza alcuna ingiustizia, ma per un suo gratuito atto di misericordia, prepara per alcuni i mezzi, pienamente efficaci, per condurli alla salvezza cui li ha predestinati ab aeterno. Accusato dai pelagiani di manicheismo, A. tuttavia, come si vede, non considera come malvagia la stessa natura umana, e non condanna la procreazione: nel matrimonio, il male Ăš la concupiscentia carnis; e anche questo puĂČ essere rivolto a un fine buono, la generazione dei figli congiunta alla volontĂ della loro rigenerazione attraverso il battesimo. Ma i bambini morti senza di questo, secondo A., non si sottraggono alla pena eterna. PoichĂ© la trasmissione del peccato originale si spiegava piĂč facilmente mediante la teoria secondo cui l'anima Ăš generata, spiritualmente, da quella dei genitori (traducianismo), mentre, piĂč conforme alla sua dottrina dell'illuminazione, era l'altra teoria, della creazione di ogni anima da Dio (creazionismo), A. rimase incerto fino all'ultimo (De anima et eius origine, 419-20). E poichĂ© Ăš ignoto chi siano gli eletti, la concezione agostiniana della predestinazione coincide con quella della Chiesa come corpus permixtum (v. sopra). La scossa profonda data a tutto il mondo romano dall'incursione di Alarico, le querimonie dei pagani additanti nel cristianesimo la causa di tutti i mali del mondo, indussero A. a meditare sulla storia, e a scrivere l'altra delle sue opere maggiori e piĂč celebri dopo le Confessioni: il De civitate Dei. Nel corso della storia procedono unite le due cittĂ (Civitas Dei e Civitas terrena), nate l'una dall'amor Dei usque ad contemptum sui, l'altra dall'amor sui usque ad contemptum Dei e predestinate, la prima a regnare in eterno con Dio, l'altra a subire l'eterno supplizio. Neppure quest'opera Ăš, in fondo, davvero sistematica; cosciente dello sviluppo del proprio pensiero, A. sembra invitare i lettori a imitarlo nello sforzo di progredire: del resto volle egli stesso correggere i suoi errori (ma anche dimostrare, specie contro i manichei, la sua fondamentale coerenza) in quella originalissima rassegna dei suoi scritti che sono le Retractationes (426-27). Va menzionato ancora, breve e bellissimo compendio della dottrina cristiana, l'Enchiridium ad Laurentium (De fide, spe, charitate, 421); e va almeno accennato il valore letterario dei suoi scritti, specie delle Confessioni. Festa, 28 agosto. L'interesse educativo di A. non Ăš limitato ai problemi pedagogici piĂč dibattuti dalla Patristica, e cioĂš all'utilizzazione della cultura pagana nella formazione dei ragazzi, ed ai modi e metodi dell'educazione religiosa. Esso si connette piuttosto ad un tema filosofico fondamentale nella sua speculazione, quello della "veritĂ interiore" e quindi con la dottrina dell'illuminazione. Il processo educativo consiste nel trarre alla luce la veritĂ , nel ritrovare Dio-maestro nel profondo dell'anima (Christus intus docet). Il maestro vero Ăš quindi solo Cristo, i maestri terreni non possono far altro che stimolare la riscoperta della veritĂ stessa che Ăš in noi come segno della presenza di Dio. Dal punto di vista didattico A. accoglie la necessaria propedeutica delle "arti liberali", ma la cultura per sĂ© non Ăš indispensabile, poichĂ© le virtĂč cristiane si realizzano anche al di fuori di esse. Necessaria Ăš invece la cultura religiosa da impartire anche alle menti piĂč rozze: nel De catechizandis rudibus Agostino parla di tale opera educativa, ponendo in rilievo la funzione fondamentale che ha in essa l'amore con cui il maestro discende al livello dell'educando (cosĂŹ come Cristo ha fatto per l'uomo facendosi uomo) e vivifica anche gli aspetti piĂč elementari e consueti del fatto educativo.
EVALUER LE RISQUE CLIENT I Les enjeux liĂ©s au risque client II la prise de renseignements pendant la phase commerciale III LâĂ©valuation de la solvabilitĂ© dâun prospect ou client 1. A partir du bilan comptable 2. A lâaide dâindicateurs internes IV Les outils dâĂ©valuation des risques I Les enjeux liĂ©s au risque client 1. DĂ©finition et critĂšres de risques On entend par risque client lâensemble des situations dans lesquelles le client pourrait compromettre la pĂ©rennitĂ© du fournisseur. Quelques critĂšres permettent de repĂ©rer le risque client : - la taille et lâĂąge de lâentreprise - le produit quâelle propose, - son client avec ses propres clients (la sous traitance par exemple induit un lien de dĂ©pendance) - le secteur sur lequel elle Ă©volue - la concurrence quâelle subit - et le montant de ses disponibilitĂ©s On peut ainsi rĂ©partir les degrĂ©s de risque : 2. Les impayĂ©s clients : premiĂšre cause de faillite des entreprises Par principe, lâentreprise dĂ©pense avant dâencaisser. En accordant des dĂ©lais de paiement, elle se prive de trĂ©sorerie. Elle a alors un besoin en fonds de roulement (BFR), c'est-Ă -dire besoin de disposer dâune trĂ©sorerie dâavance. Tout retard de paiement engendre donc une augmentation du BFR que lâentreprise nâest parfois plus en Ă©tat de couvrir (dĂ©couvert bancaire).Lorsque le client est insolvable, câest un manque de trĂ©sorerie qui pĂšse sur lâentreprise et donc sur sa pĂ©rennitĂ©. La PME limite donc les risques si certains de ses clients payent comptant. Les entreprises activent donc plusieurs stratĂ©gies pour faire face Ă leurs impayĂ©s : 29% gĂšrent les relances en interne, 24% nĂ©gocient des facilitĂ©s de caisse avec leur banque et 19% nĂ©gocient avec les fournisseurs. II la prise de renseignements pendant la phase commerciale Lâentreprise qui souhaite conclure un contrat avec un prospect professionnel peut consulter un certain nombre de documents disponibles auprĂšs dâorganismes. Les organismes les plus sollicitĂ©s sont : - la greffe du tribunal de commerce : elle dĂ©livre gratuitement des informations sur les entreprises immatriculĂ©es au registre du commerce et des sociĂ©tĂ©s telles que les statuts, les comptes annuels, lâĂ©tat dâendettement, lâextrait kbis. L'extrait Kbis reprĂ©sente la vĂ©ritable « carte d'identitĂ© » Ă jour d'une entreprise immatriculĂ©e au Registre du Commerce et des SociĂ©tĂ©s (RCS). - les sociĂ©tĂ©s spĂ©cialisĂ©es fournissent des informations commerciales et financiĂšres, des documents comptables et des analyses payantes permettant de vĂ©rifier lâĂ©tat de santĂ© des entreprises : - les cabinets de recouvrement et sociĂ©tĂ©s dâassurance : ils rĂ©alisent des enquĂȘtes de solvabilitĂ© et Ă©mettent un avis sur le risque de dĂ©faillance sous forme de score ou de note. - Les banques : les entreprises sont notĂ©es par les banques. La cotation de la banque mesure la capacitĂ© de lâentreprise Ă honorer ses engagements financiers sur 3 ans. GrĂące Ă cette cotation, la PME peut ainsi , par lâintermĂ©diaire de la banque, vĂ©rifier si le prospect ou client est solide financiĂšrement. III LâĂ©valuation de la solvabilitĂ© dâun prospect ou client La solvabilitĂ© correspond Ă la capacitĂ© de lâentreprise Ă faire face Ă ses engagements Ă long terme. Lâentreprise est solvable si la valeur de ses actifs (immobilisations, crĂ©ances, stocks et disponibilitĂ©s) est supĂ©rieure Ă ses emprunts et dettes. Une entreprise peut ĂȘtre solvable mais peut manquer de liquiditĂ©s, c'est-Ă -dire dâargent disponible au quotidien. La liquidĂ© mesure donc la capacitĂ© de lâentreprise Ă faire face Ă ses engagements Ă court terme. 1. A partir du bilan comptable Le bilan comptable fournit des indications sur la santĂ© financiĂšre de lâentreprise prospect Les dĂ©finitions que vous devez maitriser : âą Pour lâactif : Câest quoi une Immobilisation ? La notion d'immobilisation intĂšgre l'ensemble des biens durables dĂ©tenus par une entreprise sur plus d'un exercice comptable et qui ne sont pas destinĂ©s Ă la revente. Les immobilisations financiĂšres correspondent aux actifs financiers d'utilisation durable possĂ©dĂ©s par l'entreprise. Il s'agit notamment des titres de participation, des prĂȘts accordĂ©s⊠Les immobilisations incorporelles comprennent les frais d'Ă©tablissement, les frais de recherche et dĂ©veloppement, les concessions, brevets, licences, marques, logiciels et autres droits similaires, le droit au bail, le fonds commercial. Une immobilisation corporelle correspond Ă un actif physique que lâentreprise entend utiliser au-delĂ de la clĂŽture de lâexercice comptable en cours : les terrains, les constructions, lâagencement et les installations gĂ©nĂ©rales, lâoutillage, le matĂ©riel, les vĂ©hicules, le mobilier et les Ă©quipements informatiques. Que signifie disponibilitĂ©s ? Le poste "DisponibilitĂ©s" est constituĂ© des montants dĂ©tenus en caisse (piĂšces et billets que l'entreprise possĂšde) et des avoirs en banque (argent dĂ©tenu sur les comptes bancaires de l'entreprise). On utilise Ă©galement le terme de trĂ©sorerie. Câest quoi une valeur mobiliĂšre de placement ? Ce sont des titres financiers, actions ou obligations. En comptabilitĂ©, elles correspondent aux excĂ©dents de trĂ©sorerie placĂ©s par l'entreprise. âą Pour le passif : Que signifie capitaux propres ? Les capitaux propres sont les ressources financiĂšres que possĂšde l'entreprise Le capital social dâune entreprise est Ă©gal au montant total des apports de biens et dâargent des associĂ©s Que signifie rĂ©serves ? Cumul des bĂ©nĂ©fices des exercices antĂ©rieurs qui n'ont pas Ă©tĂ© redistribuĂ©s aux propriĂ©taires de l'entreprise, ni intĂ©grĂ©s dans son capital Que signifie rĂ©sultat ? Il correspond aux ressources restantes Ă l'entreprise une fois les charges dĂ©duites du chiffre d'affaires. 2 A lâaide dâindicateurs internes Une entreprise manque souvent de temps et de moyens pour suivre lâensemble des ses encours clients. Toutefois, il est nĂ©cessaire dâanalyser rĂ©guliĂšrement certains supports pour anticiper les problĂšmes de trĂ©sorerie. Elle peut - analyser son portefeuille clients via la mĂ©thode ABC (vu dans un chapitre prĂ©cĂ©dent), - prendre du recul sur les retards de paiement : le service comptable signale les retards de paiement ou les demandes rĂ©guliĂšres de report dâĂ©chĂ©ances. La balance ĂągĂ©e permet de visualiser les clients Ă relancer Exemple : - mettre en place des indicateurs de suivi des impayĂ©s via un tableau Excel Exemple : IV Les outils dâĂ©valuation des risques Les entreprises peuvent se procurer des logiciels dĂ©diĂ©s au risque client mais il sont souvent trĂšs complexes Ă utiliser. Certaines entreprises utilisent le crĂ©dit management : câest lâensemble des procĂ©dures financiĂšres ou juridiques visant Ă optimiser le chiffre dâaffaires de lâentreprise en accĂ©lĂ©rant les rĂšglements clients. Une des mĂ©thodes de crĂ©dit management sâappelle la mĂ©thode des points de risque. Elle consiste Ă classer les clients selon leur risque afin de leur fixer des modalitĂ©s de paiement adaptĂ©s. Elle permet donc dâĂ©valuer les risques de coopĂ©ration et de se prĂ©munir au cas par cas. Exemple de tableau des points de risque
I DĂ©finition La proposition commerciale est une offre adressĂ©e Ă un client ou prospect suite Ă sa demande. Le commercial doit donc veiller Ă soigner sa prĂ©sentation, car la proposition commerciale est la vitrine de lâentreprise La proposition commerciale est le support de la relation entre lâentreprise et le client/prospect. II La finalitĂ© dâune proposition commerciale La proposition commerciale permet de rĂ©pondre prĂ©cisĂ©ment aux attentes du client qui souhaite passer une commande. Dans cette optique, la proposition doit ĂȘtre : - claire, - personnalisĂ©e - diffĂ©renciĂ©e de celles de la concurrence. La proposition commerciale permet Ă©galement de renseigner le client non pas uniquement sur les prestations proposĂ©es mais aussi sur lâentreprise elle-mĂȘme grĂące Ă son numĂ©ro dâidentification (SIRET) dĂ©livrĂ© par lâINSEE III Le systĂšme dâinformation client Pour rĂ©aliser la proposition commerciale, le commercial doit collecter des informations sur la clientĂšle, sur les produits mais Ă©galement sur lâenvironnement commercial. Elle consulte donc le systĂšme dâinformation client dont lâacronyme est SIC. Il est constituĂ© de fichiers commerciaux utilisables par tous les collaborateurs de lâentreprise afin dâamĂ©liorer la connaissance de la clientĂšle et des propsects. Son contenu est le suivant : IV Les logiciels pour prĂ©parer une proposition commerciale. Il est possible de prĂ©parer les propositions commerciales sur un texteur, un tableur, un logiciel spĂ©cialisĂ© en gestion commerciale ou un progiciel de gestion intĂ©grĂ© : Logiciels pouvant ĂȘtre utilisĂ©s Traitement de texte (Word, Open Writer, etc.) Tableur (Excel, Open Calc, etc.) Logiciel de gestion commerciale (EBP, Ciel, etc.) PGI (Cegid, Sage, EBP) Si lâentreprise possĂšde un PGI ou un logiciel de gestion commerciale, la proposition commerciale sera effectuĂ©e sur ce type de logiciel. Dans le cas contraire, il est recommandĂ© dâutiliser le tableur. Le progiciel est lâoutil privilĂ©giĂ© par les entreprises car il regroupe un ensemble de logiciels (modules) intĂ©grant les principales fonctions nĂ©cessaire Ă la gestion des flux monĂ©taires et physiques de lâentreprise. Tous ces modules accĂšdent Ă des ressources communes, stockĂ©es dans une base de donnĂ©es unique. Les modules les plus courants sont : Ainsi, le PGI permet dâĂ©viter les saisies redondantes, qui sont sources dâerreurs et de perte de temps. V Distinguer devis et proposition commerciale 1. Le devis Câest une offre adressĂ©e Ă un client ou un prospect destinĂ©e Ă rĂ©pondre Ă son besoin suite Ă la demande du client. Son contenu se limite souvent Ă la rĂ©fĂ©rence des produits et leurs prix. Le devis est donc un engagement de lâentreprise pour rĂ©aliser une prestation ou pour dĂ©livrer un produit au prix indiquĂ© et dans les dĂ©lais annoncĂ©s. Seules la signature du client et la date donnent au devis la valeur juridique dâun contrat. Il peut donc ajouter « Lu et acceptĂ© » ou encore « bon pour travaux » par exemple. 2. La proposition commerciale Par rapport au devis, la proposition commerciale nĂ©cessite une analyse plus poussĂ©e des besoins du client, un chiffrage de lâoffre plus complexe et un document plus personnalisĂ© VI Les Ă©tapes pour rĂ©aliser une offre commerciale Les Ă©tapes de la mise en Ćuvre dâune proposition commerciale sont : â lâanalyse des besoins du client ; â la recherche des informations qui permettent dâĂ©tablir lâoffre correspondant aux besoins du client (prix, dĂ©lai de livraison, planning de production, etc.) ; â la mise en forme de la proposition : On peut donc la schĂ©matiser ainsi : VII Les mentions obligatoires Ă faire figurer sur la proposition commerciale VIII Les sanctions en cas de non respect des mentions obligatoires Tout manquement peut aboutir Ă une contravention pouvant aller jusquâĂ 1500 ⏠dâamende.
I. DĂ©finition L'appel d'offres est donc une procĂ©dure par laquelle un acheteur public choisit l'offre Ă©conomiquement la plus avantageuse, sans nĂ©gociation, sur la base de critĂšres objectifs prĂ©alablement dĂ©finis Son but est de mettre en concurrence plusieurs entreprises privĂ©es pour obtenir la meilleure offre possible. Les caractĂ©ristiques principales sont les suivantes : âą Absence de nĂ©gociation : L'acheteur sĂ©lectionne l'offre uniquement sur la base des propositions reçues, sans nĂ©gociation avec les candidats âą CritĂšres objectifs : La sĂ©lection se fait selon des critĂšres dĂ©finis Ă l'avance et communiquĂ©s aux candidats âą Transparence : Les appels d'offres publics sont soumis Ă des rĂšgles strictes de publicitĂ© et de transparence Ce principe dâappel dâoffre garantie donc lâĂ©galitĂ© de traitement des entreprises privĂ©es candidates et une certaine transparence. II. Les diffĂ©rentes formes dâappel dâoffres Il existe deux formes principales d'appels d'offres dans les marchĂ©s publics : âą Appel d'offres ouvert : Toute entreprise intĂ©ressĂ©e peut rĂ©pondre Ă lâappel dâoffre âą Appel d'offres restreint : Seuls les candidats prĂ©sĂ©lectionnĂ©s par l'acheteur sont autorisĂ©s Ă soumettre une offre. Cette procĂ©dure est particuliĂšrement adaptĂ©e aux marchĂ©s complexes ou spĂ©cialisĂ©s, oĂč l'acheteur souhaite prĂ©sĂ©lectionner les entreprises les plus qualifiĂ©es avant d'examiner leurs offres en dĂ©tail. III. Les objectifs pour une PME de prospecter des nouveaux marchĂ©s via les appels dâoffres Il y a plusieurs objectifs pour une entreprise de prospecter de nouveaux marchĂ©s : â trouver de nouveaux clients ; â garantir le dĂ©veloppement de lâactivitĂ© de lâentreprise ; â compenser lâĂ©rosion du portefeuille clients existant ou remplacer les clients peu ou pas rentables Ainsi, au-delĂ du simple gain commercial, les appels d'offres reprĂ©sentent un vĂ©ritable levier stratĂ©gique de dĂ©veloppement pour les entreprises, quelle que soit leur taille. IV. La procĂ©dure de rĂ©ponse aux appels dâoffre 1. Les Ă©tapes principales Voici les principales Ă©tapes pour rĂ©pondre efficacement Ă un appel d'offres : âą Identifiez les appels d'offres pertinents âą Activez des alertes automatiques sur les plateformes dĂ©diĂ©es âą TĂ©lĂ©chargez le Dossier de Consultation des Entreprises (DCE) âą Analysez minutieusement le cahier des charges et le rĂšglement de consultation âą PrĂ©parer la rĂ©ponse soit constituez le dossier de candidature avec les documents administratifs requis âą Transmettre la rĂ©ponse soit dĂ©poser le dossier complet sur la plateforme de dĂ©matĂ©rialisation avant la date limite âą Suivre la rĂ©ponse : en cas de rejet, demandez un retour pour identifier les points d'amĂ©lioration 2. La consultation des appels dâoffre Les PME doivent dâabord identifier les appels d'offres pertinents. Cela peut se faire par : âą Les rĂ©seaux professionnels : Participer Ă des salons, des confĂ©rences et des Ă©vĂ©nements rĂ©seaux aide Ă dĂ©couvrir des opportunitĂ©s. âą La veille : S'abonner Ă des bulletins d'information et des alertes sur les marchĂ©s pertinents. âą La consultation de plateformes en ligne : De nombreux sites web rĂ©pertorient les appels d'offres publics, utilisateur aux PME de filtre par secteur et localisation. Lâassistant(e) de gestion dispose de plusieurs sites de marchĂ© publics Voici les principaux sites français pour consulter les appels d'offres publics : Les Sites officiels : ïŒ BOAMP (Bulletin Officiel des Annonces des MarchĂ©s Publics) : C'est le site officiel qui publie les appels d'offres de l'Ătat, des collectivitĂ©s territoriales et des Ă©tablissements publics ïŒ PLACE (Plateforme des Achats de l'Ătat) : C'est la plateforme de dĂ©matĂ©rialisation des marchĂ©s publics de l'Ătat. La publication y est obligatoire pour les marchĂ©s de l'Ătat Ă partir de 40 000 ⏠HT ïŒ JOUE (Journal Officiel de l'Union EuropĂ©enne) : Il publie les appels d'offres europĂ©ens Les plateformes privĂ©es : ïŒ France MarchĂ©s : Ce portail agrĂšge les appels d'offres de plus de 300 journaux rĂ©gionaux, du BOAMP, du JOUE et de plus de 1000 sites d'acheteurs publics ïŒ MarchĂ©s Online : Cette plateforme donne accĂšs Ă l'ensemble des appels d'offres publiĂ©s, quel que soit le secteur d'activitĂ© ïŒ E-marchespublics : Ce site permet d'accĂ©der aux appels d'offres publiĂ©s sur diverses sources comme le BOAMP, le JOUE, la presse et les profils d'acheteurs Les Autres sources : ïŒ Journaux d'Annonces LĂ©gales (JAL) : Environ 540 journaux en France sont habilitĂ©s Ă publier des annonces lĂ©gales, dont les appels d'offres ïŒ Sites internet des administrations publiques : La plupart des administrations publient leurs appels d'offres directement sur leur site internet ïŒ Presse spĂ©cialisĂ©e : Certaines revues sont spĂ©cialisĂ©es dans les appels d'offres de leur dĂ©partement ou rĂ©gion Pour une veille efficace, il est recommandĂ© d'utiliser des outils de veille Ă©lectronique ou de s'abonner aux alertes proposĂ©es par ces diffĂ©rentes plateformes. Cela permet de recevoir automatiquement les appels d'offres correspondant Ă vos critĂšres de recherche 3. Les candidatures dâappels dâoffre Pour concourir Ă un marchĂ© public, il est possible de se prĂ©senter seul, de prĂ©senter une candidature groupĂ©e avec plusieurs entreprises : âą La candidature seule : l'entreprise se prĂ©sente pour exĂ©cuter personnellement le marchĂ©. Elle a la capacitĂ© technique et financiĂšre dâexĂ©cuter seule et dans son entier le marchĂ©. âą Le groupement : le groupement conjoint (lâentreprise n'est responsable que de la part du marchĂ© qu'elle exĂ©cute) ou le groupement solidaire : (chaque membre du groupement est engagĂ© financiĂšrement pour la totalitĂ© du marchĂ©. Cela signifie que tous les membres sont collectivement responsables de l'exĂ©cution complĂšte du contrat). 4. La rĂ©ponse Ă lâappel dâoffre La rĂ©ponse Ă un appel d'offres doit contenir les Ă©lĂ©ments suivants : âą une lettre de prĂ©sentation : PrĂ©senter briĂšvement l'entreprise et son intĂ©rĂȘt pour le projet. âą une proposition technique : DĂ©tails sur la façon dont le projet sera rĂ©alisĂ© soient les mĂ©thodes et leurs chronologies. âą Une proposition financiĂšre : faire une estimation des coĂ»ts et des conditions de paiement Le dossier de rĂ©ponse Ă©tant lâinterface entre la PME et le donneur dâordre, il convient de lui apporter le plus grand soin. Il faut donc prĂ©parer le dossier de rĂ©ponse et remplir le document unique de marchĂ© europĂ©en appelĂ© DUME : dĂ©claration sur l'honneur standardisĂ©e et Ă©lectronique utilisĂ©e dans les procĂ©dures de marchĂ©s publics Le certificat Ă©lectronique est un Ă©lĂ©ment essentiel pour rĂ©pondre aux appels d'offres publics dĂ©matĂ©rialisĂ©s. Voici les principaux points Ă retenir : ïŒ Depuis le 1er octobre 2018, la dĂ©matĂ©rialisation est obligatoire pour les marchĂ©s publics supĂ©rieurs Ă 40 000 ⏠HT ïŒ Dans ce cadre, une signature Ă©lectronique valide est requise pour signer les documents de rĂ©ponse aux appels d'offres. L'utilisation d'un certificat Ă©lectronique pour les appels d'offres prĂ©sente plusieurs avantages : ïŒ Gain de temps dans les Ă©changes avec les acheteurs publics ïŒ Ăconomies sur les frais d'impression et d'envoi ïŒ SĂ©curisation accrue des documents transmis ïŒ PossibilitĂ© de signer Ă distance Les certificats Ă©lectroniques pour rĂ©pondre aux appels d'offres sont dĂ©livrĂ©s par des prestataires de services de confiance qualifiĂ©s, conformes au rĂšglement europĂ©en eIDAS et au RĂ©fĂ©rentiel GĂ©nĂ©ral de SĂ©curitĂ© (RGS) français. Les principaux Ă©metteurs de ces certificats sont : ïŒ CertEurope ïŒ ChamberSign France ïŒ Certigna (filiale de Docaposte) ïŒ Dhimyotis ïŒ Universign La date limite de rĂ©ception des offres (DLRO) est un Ă©lĂ©ment crucial dans le processus des appels d'offres pour les marchĂ©s publics. La DLRO, Ă©galement appelĂ©e date limite de remise des offres ou des plis, correspond Ă la date et l'heure limites auxquelles les candidatures ou offres doivent ĂȘtre reçues par l'acheteur public1 Le dĂ©lai commence le lendemain de la date d'envoi de l'avis d'appel Ă la concurrence par l'acheteur. Dans cette dĂ©marche, lâentreprise peut rĂ©aliser un tableau de suivi des appels dâoffres dont voici un exemple : 5. La rĂ©ponse Ă lâappel dâoffre Une fois la dĂ©cision prise, l'acheteur doit envoyer une notification officielle Ă l'entreprise retenue. Cette communication doit ĂȘtre faite par Ă©crit, gĂ©nĂ©ralement par lettre recommandĂ©e avec accusĂ© de rĂ©ception ou par voie Ă©lectronique sĂ©curisĂ©e. Tout candidat Ă©vincĂ© peut demander par Ă©crit des informations complĂ©mentaires sur les motifs du rejet de son offre. L'acheteur doit alors rĂ©pondre dans un dĂ©lai de 15 jours en fournissant : âą Les motifs dĂ©taillĂ©s du rejet de la candidature ou de l'offre âą Les caractĂ©ristiques et avantages de l'offre retenue âą Le nom de l'attributaire V. Le paiement des marchĂ©s en appel dâoffres Le dĂ©lai maximal de paiement est gĂ©nĂ©ralement de 30 jours. Ce dĂ©lai est portĂ© Ă 50 jours pour les hĂŽpitaux et 60 jours pour les entreprises publiques. . Le paiement intervient aprĂšs constatation du "service fait", c'est-Ă -dire une fois que la prestation a Ă©tĂ© rĂ©alisĂ©e et vĂ©rifiĂ©e conforme par l'acheteur public Des avances et acomptes peuvent ĂȘtre versĂ©s : ïŒ L'avance est obligatoire pour les PME sur les marchĂ©s de plus de 50 000 ⏠HT et d'une durĂ©e supĂ©rieure Ă 2 mois. Elle reprĂ©sente 20% du montant pour l'Ătat, 10% pour les autres acheteurs publics ïŒ Les acomptes sont versĂ©s tous les 3 mois maximum, ou tous les mois pour les marchĂ©s de travaux avec des PME
Received: 26 November 2019 Revised: 10 January 2020 Accepted: 19 January 2020 DOI: 10.1111/obr.13005 PEDIATRICS/PHYSIOLOGY Adipokines: A gear shift in puberty DesirĂ©e Nieuwenhuis | NatĂ lia Pujol-Gualdo Amanda J. Kiliaan Department of Anatomy, Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Preclinical Imaging Center PRIME, Nijmegen, The Netherlands Correspondence Amanda J. Kiliaan, PhD, Associate Professor, Department of Anatomy, Donders Institute for Brain, Cognition, and Behaviour, Preclinical Imaging Center PRIME, Radboud university medical center, 6500 HB Nijmegen, Geert Grooteplein 21N 6525 EZ Nijmegen, The Netherlands. Email: amanda.kiliaan@radboudumc.nl Funding information Europees Fonds voor Regionale Ontwikkeling (EFRO), Grant/Award Number: BriteN 2016 1 | INTRODUCTION The prevalence of obesity in adolescents and children is increasing in | Ilse A.C. Arnoldussen | Summary In this review, we discuss the role of adipokines in the onset of puberty in children with obesity during adrenarche and gonadarche and provide a clear and detailed overview of the biological processes of two major players, leptin and adiponectin. Adipokines, especially leptin and adiponectin, seem to induce an early onset of puberty in girls and boys with obesity by affecting the hypothalamic-pituitary- gonadal (HPG) axis. Moreover, adipokines and their receptors are expressed in the gonads, suggesting a role in sexual maturation and reproduction. All in all, adipokines may be a clue in understanding mechanisms underlying the onset of puberty in child- hood obesity and puberty onset variability. KEYWORDS adipokines, obesity, puberty 1,2 the age of 5 years were overweight or were with obesity in 2016, and 3 Obesity is defined by an excessive accumulation of white adipose tissue (WAT), and it is often indicated by a body mass index (BMI) 4 above 30. Two main types of adipose tissue were described: WAT and brown adipose tissue (BAT), which differ in morphology and func- 5-7 Ilse A.C. Arnoldussen and Amanda J. Kiliaan contributed equally to this work. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2020 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation Obesity Reviews. 2020;21:e13005. wileyonlinelibrary.com/journal/obr 1 of 10 https://doi.org/10.1111/obr.13005 alarming rates. Specifically, worldwide, 41 million children below this number is expected to increase to 70 million in 2025. obesity is associated with various severe health complications, includ- ing increased risk of diabetes mellitus type 2, hypertension, heart dis- eases, and disturbances in sex hormone levels. 5,6 and mitochondria and plays a role in thermogenesis. Adipocytes in tion. BAT consists of adipocytes containing multiple lipid droplets WAT contain only a few mitochondria and a single lipid droplet. Adipose tissue has several functions including the storage of energy, thermogenesis, and the production and secretion of adipokines Generally, two physiological processes, adrenarche and gonadarche, 11,24 Childhood 5,7,8 a key role in puberty onset. Puberty is known as a period through which the body changes physically, being a physiological process resulting in the maturation of children, i.e. they develop sexual characteristics and obtain reproduc- 9,11 Adipokines are involved in a number of physiological processes including blood pressure, metabo- lism, glucose, and vascular homeostasis and may play amongst others 8-10 (hormones, cytokines, and peptides). tive functions. between obesity and puberty,2,12-23 the biological mechanisms under- lying obesity and puberty onset remain unclear. Hereafter, we review in detail the role of adipokines in the onset of puberty in childhood obesity. Although many studies have shown associations 2 | INITIATION OF PUBERTY PHYSIOLOGICAL PROCESSES IN THE interact to regulate the onset of puberty. During adrenarche, the adrenal cortex secretes steroid hormones (including 2 of 10 NIEUWENHUIS ET AL. androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate (DHEAS), androstenedione, and cortisol), insulin-like growth factor, and growth hormone, which contribute to the pubertal insights on new genetic loci (e.g. melanocortin-4 receptor, mitochon- drial carrier 2, and mitogen-activated protein kinase 13) and on sev- eral pathways that regulate the timing of puberty; however, it partly 34 9,24,25 Both adrenarche and gonadarche are involved in the development growth spurt, body odor, skin oiliness, and skeletal maturation. explains puberty timing variation. Thereby, defining the role of 25 adipokines is of importance in elucidating the variability in puberty as the expression of adipokines is sex-specific and is altered with body composition, adiposity, and during growth spurts. Moreover, adipokines and their receptors are expressed in gonads and several brain regions suggesting involvement in the onset of puberty and sex- ual maturation. Lastly, adipokines interfere in processes regulating timing and duration of puberty, for instance in the HPA and HPG axes which are both key players during adrenarche and gonadarche. Involvement of adipokines in the onset of puberty and specifically in individuals with obesity will be further reviewed in the next 2,24 3 | Puberty onset in girls is assessed using different markers, such as thelarche (breast development), menarche (the start of of pubic hair. pituitary-gonadal (HPG) axis is activated,2,26 and several hormones have been identified to participate in the activation of the HPG axis During gonadarche (Figure 1), the hypothalamic- 2,27 Kisspeptin, neurokinin B, and dynorphin are released by specialized including kisspeptin, neurokinin B, dynorphin, leptin, and ghrelin. 28 key regulator of the pulsatile secretion of gonadotropin releasing neurons, the KNDy neurons in the hypothalamus. Kisspeptin is a 29,30 B stimulates, and dynorphin inhibits the release of kisspeptin, which hormone (GnRH) from the hypothalamus. In addition, neurokinin implies that both coordinate a pulsatile release of kisspeptin. 31 Sub- sections. sequently, the activated HPG axis induces the pituitary gland to secrete luteinising hormone (LH) and follicle stimulating hormone (FSH). As a result, gametogenesis occurs, and the gonads will release sex hormones. Consequently, secondary sex characteristics develop including breast development in girls and an increased testicular vol- 2,26,32 is possibly due to differences in levels of body fat, hypothalamic-pitui- THE ONSET OF PUBERTY IN GIRLS ume in boys. The age at puberty onset varies greatly among individuals, which 19 35 menstruation), and pubic hair development. 33 genome-wide association studies have provided important new tary-adrenal (HPA) axis activity, and genetic background. Recent The average age of However, this age differs between cultures and ethnicities, and since 1980, age at menarche is girls at start of menarche is 12.4 years. 36 significantly decreasing. 36-39 F I G U R E 1 Hormonal regulation in the initiation of puberty in boys and girls. The secretion of kisspeptin, neurokinin B, and dynorphin from KNDy neurons initiate the release of gonadotropin releasing hormone (GnRH) from the hypothalamus. This activates the pituitary gland to produce and secrete luteinising hormone (LH) and follicle stimulating hormone (FSH), which in turn stimulate the gonads to produce estrogen and testosterone in girls and boys, respectively 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License NIEUWENHUIS ET AL. 3 of 10 T A B L E 1 Summary of included studies Authors Year Country Study Design Primary Outcome Sex Sample Size (n) Age (y) Data Collection Lian et al21 2019 China Cross-sectional Puberty starts earlier in Chinese Han girls with obesity compared with Chinese Han girls with normal weight. Girls 2996 9-19 2012 and 2013 Biro et al12 Lazzeri et al20 2018 USA 2018 Italy Longitudinal Cross-sectional Body mass index had a greater effect on age at menarche than did race and ethnicity. Girls 946 6-16 2004-2014 Li et al23 2018 China Longitudinal For both, boys and girls, a higher BMI (ie, overweight and obese) is associated with earlier onset of puberty Girls Girls Boys Girls 542 Deng et al22 Flom et al15 2017 China Cross-sectional Increased BMI is associated with early timing spermarche and menarche. Boys Girls Girls 1278258 9-15 2005-2012 He et al24 Holmgren et al17 2017 China 2017 Sweden Cross-sectional Longitudinal Onset of puberty is not related to obesity in boys. Boys Boys Girls Girls 782 7-17 972 929 5839 Kelly et al19 2017 UK 2016 Brazil 2016 USA Longitudinal prospective cohort Higher BMI in girls is associated with the onset of menstruation at an earlier age. 11 10-18 11-17 Barcellos Gemelli et al25 Cross-sectional Longitudinal Excess weight is associated with early age of menarche. Girls 727 2014 2003-2009 Glass et al16 Lee et al26 In girls, but not in boys, greater adiposity is associated with the earlier onset of puberty. Boys Girls 135 Cabrera et al27 Leonibus et al14 2014 USA 2013 Italy Cross-sectional Longitudinal Thelarche occurred earlier than recently reported, while age of menarche remained unchanged. Girls 610 3-17.9 2007 2005-2012 Currie et al13 2012 Europe, USA, Canada Cross-sectional Overweight/obesity during childhood predicts the early onset of puberty in girls. Girls 20410 11, 13, 15 2005-2006 2017 USA Prospective birth cohort Overweight/obese status at the age of 7 ye was associated with increased risk of early menarche 788 From birth to menarche occurred Pregnancies 1959-1966 2016 USA Cross-sectional Boys with overweight enter puberty earlier compared with boys with normal weight or obesity, while puberty starts later in boys with obesity compared with boys with normal weight and overweight. Boys 3872 6-16 2005-2010 Overweight during childhood shows a relation with the early onset of puberty in girls. 6535 4259 695 11 15 5.8-12.2 2009/2010 2013/2014 2014-2017 Higher BMI during childhood is associated with early puberty. 2008 and 2009 2000-2002 Obesity during childhood is related to the earlier onset of puberty. Boys Girls 84 123 71 (Continues) 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 4 of 10 NIEUWENHUIS ET AL. 3.1 | Fat storage For the initiation of puberty, the timing of stimulation and/or inhibi- tion of different hormones is important, and additionally, a certain amount and distribution of body fat is needed in order to start menar- che, which emphasizes the importance of body fat. From an evolution- ary point of view, body fat increases in mammalian females during puberty onset, and it highlights the need to guarantee a healthy preg- 40 women with anorexia nervosa. particularly body fat localized predominantly on the gluteofemoral fat depots, is profoundly associated with start of menarche, more than nancy, offspring, and maternal survival. fat, sex-hormones, and neuroendocrine alterations can evolve in men- strual dysfunction, for instance, in women with severe obesity or in 41-43 44-46 to gluteofemoral fat depots suggesting that leptin may convey infor- amount of total body fat. mation on body fat distribution to the hypothalamus during puberty. An improper level of body Importantly, body fat distribution, Blood leptin levels are strongly related 45 3.2 | HPG axis The HPG axis is activated by the release of kisspeptin resulting in the release of GnRH from the hypothalamus, and LH and FSH from the pituitary gland. In girls, FSH is involved in the development of the folli- cles in the ovaries, and it promotes the secretion of estrogen. LH stim- ulates the production of androgen hormones and induces ovulation 48 9,47 the release of kisspeptin and neurokinin B, and kisspeptin thereby (Figure 1). The secretion of estrogen has an inhibitory effect on inhibits the GnRH release from the hypothalamus. pattern of GnRH is important for the regulation of the menstrual cycle. This roughly 28-day-cycle comprises several phases, including the follicular phase and luteal phase. During the follicular phase, increasing levels of FSH stimulate the maturation of follicles and the production of estrogen from the ovaries. This in turn inhibits the release of FSH from the pituitary gland. A high level of estrogen will induce the production of LH by the pituitary gland, resulting in ovula- tion. The matured follicle secretes progesterone thereby inhibiting the release of GnRH. When the corpus luteum is demolished, there is less 48 3.3 | Adipokines According to results from studies reported in Table 1, girls with obe- sity enter puberty earlier compared with girls with normal higher leptin concentrations inhibit the intake of food and increases inhibition of GnRH. As a consequence, the cycle will start again. whole process, starting from the activated HPG axis, results in the development of the secondary sex characteristics in girls including 9,47 thelarche and menarche. 13,14,16-23,49-51 weight. these girls might be found in the secretion of adipokines. For instance, leptin is positively associated with the amount of body fat. Generally, energy expenditure. 9,52-54 An explanation for the early onset of puberty in The expression This TABLE 1 (Continued) Authors Year Country Study Design Primary Outcome Sample Sex Size (n) Age (y) Data Collection Herman-Giddens et al28 2012 USA Cross-sectional Observed mean ages of beginning genital and pubic hair growth and early testicular volumes were earlier than in past studies, depending on the characteristic and race/ethnicity. Boys 4131 6-16 2005-2010 Sorensen et al29 Aksglaede et al30 2010 2009 Denmark Denmark Cross-sectional/longitudinal Longitudinal Puberty onset at earlier ages was associated with an increased BMI in boys. Boys 1528 5.8-19.9 1991-1993/2006-2008 1930-1969 Juul et al31 Ribeiro et al32 2007 2006 Denmark Portugal Retrospective cohort Cross-sectional Higher BMI is associated with early voice break. 11-15 10-15 1990-1999 Kaplowitz et al18 Abbreviation: BMI, body mass USA Cross-sectional The early onset of puberty in Caucasian girls is likely related to an increased BMI. 5-12 1992-1993 2001 index. The higher BMI in boys and girls at 7 y of age, the earlier they enter puberty. Boys 21 612 Girls 135 223 Boys 463 Boys 382 Girls 437 Girls 10 750 Early sexual maturation in boys and girls is associated with overweight. 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License NIEUWENHUIS ET AL. 5 of 10 Leptin may possibly play a role in adrenarche as its plasma level increases with higher levels of body fat and as it can modulate both girls. 33 ing adrenarche. In coherence, in children with obesity, the androgen These findings suggested that lower reproductive status was associated with higher total adiponectin concentrations and that a higher reproductive status was related to higher HMW adiponectin the HPA and HPG axes. These axes are functionally integrated dur- DHEAS was positively associated with leptin levels. Nevertheless, concentrations in girls. In addition, individuals with obesity often another study showed that enhanced adrenal androgen secretion in girls with premature adrenarche was not explained by leptin or BMI 55 ated with androgen levels in girls ; however, it was not related to levels. and IL-6. TNF-α alters, and IL-6 inhibits the expression of 56 8 In addition, the adipokine adiponectin was negatively associ- 57 differences of adiponectin seem to develop during the progression of 56 adiponectin (Figure 2). Thereby, a low level of total adiponectin and/or high levels of inflammatory cytokines in individuals with obe- sity can promote the onset of puberty. Many more adipokines are secreted by WAT including omentin, 52,65-67 9,36,62,68 adrenarche in girls with Prader-Willi syndrome. Interestingly, sex puberty. adrenarche; however, both are not required factors. Thus, leptin and adiponectin might be able to influence In gonadarche, leptin can stimulate the secretion of kisspeptin, and subsequently activation of the HPG axis, which eventually increases the expression of estrogen and androstenedione in the ova- 58 2,60 65-67 The expression of these ries (Figure 2). Ob gene in WAT, resulting in the synthesis and secretion of leptin. Thus, high levels of leptin promote onset of puberty in girls via secre- tion of kisspeptin, and estrogen stimulates leptin secretion addition- ally. Moreover, adiponectin can affect the HPG axis due to the expression of adiponectin receptors in the hypothalamus, pituitary In return, estrogen stimulates the expression of the 59 gland, and gonads. onset as it inhibits the secretion of kisspeptin and GnRH in the hypo- thalamus and the release of GH and LH in the pituitary gland, and 2,60-62 52,60 63 girls with central precocious puberty (CPP). Moreover, total adiponectin had negative correlations with progression of puberty in girls (defined by Tanner stages), whereas HMW adiponectin had FIGURE 2 Adipokinesaffectingthe initiation of puberty in girls. Leptin stimulates the release of kisspeptin in KNDy neurons, which activates the hypothalamus to produce gonadotropin releasing hormone (GnRH). In response to the release of GnRH, the pituitary gland secretes follicle stimulating hormone (FSH) and luteinising hormone (LH), which stimulates the ovaries to release estrogen resulting in the formation of secondary sex characteristics in girls. Estrogen stimulates the production of leptin. Adiponectin inhibits GnRH release resulting in reduced levels of GnRH and thereby a delayed onset of puberty. TNF- α and IL-6 inhibit the production of adiponectin and therefore stimulate the onset of puberty In detail, adiponectin is a regulator of puberty thereby inhibiting the onset of puberty (Figure 2). with obesity often have low levels of adiponectin. et al. showed that total adiponectin was significantly lower, whereas high molecular weight (HMW) adiponectin was significantly higher in ment. 55 63 develop a chronic low-grade inflammatory state, which can be indi- cated by a high level of circulating inflammatory cytokines like TNF-α 64 Individuals Sitticharoon positive associations with LH levels and the progression of puberty in 63 visfatin, resistin, and chemerin. and visfatin are expressed in the ovaries. adipokines in the ovaries suggests a role within the reproductive sys- tem; however, the exact biological processes have to be examined. Thus, specifically leptin, adiponectin, and inflammatory cytokines pro- duced by WAT could be permissive key players during an early onset of puberty in girls with obesity. As an exception, HMW adiponectin seems to have a stimulatory effect on peripheral repro- ductive function as HMW is not able to cross the blood brain 63 barrier. 4 | Markers that are used to assess puberty onset in boys are THE ONSET OF PUBERTY IN BOYS spermarche, voice break, testicular volume, and pubic hair develop- 35 spermarche develop in the early stages of puberty onset, voice In women, omentin, chemerin, While pubic hair development, larger testicular volume, and 69 testicular volume increases, which occurs at an average age of break usually appears in later stages of puberty. Generally, first 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 6 of 10 NIEUWENHUIS ET AL. 11.9 years, followed by the development of pubic hair at 12.2 years of average, and lastly, boys experience spermarche around an aver- 55 related with leptin levels. Thereby, leptin plausibly has a minor impact in adrenarche in boys. Since leptin receptors are found in the hypothalamus, pituitary gland, and testes, they might be involved in the onset of puberty by affecting the HPG axis during gonadarche. Leptin stimulates the release of kisspeptin and GnRH, and as a consequence, it accelerates the onset of puberty (Table 1, Figure 3). In contrast, adiponectin inhibits the secretion of GnRH, GH, LH, and FSH therewith delaying the onset of puberty. However, adiponectin levels are generally lower in men compared with women and even lower in men with obe- age age of 13.4 years. 70 4.1 | Fat storage Many aspects of the reproductive physiology are energetically demanding,71 and therefore, an adequate energy level is necessary. In boys, a dynamic change in body composition occurs around the age of 10 to 13 years, in which they gain approximately 40% of sity. culating inflammatory cytokines. levels can stimulate the HPG axis and therewith an early onset of puberty in boys. Nevertheless, leptin can inhibit the production of tes- 72 mostly consisting of lean mass, which causes exhaustion of most of fat. Subsequently, a growth spurt follows in which they gain tissue 72 in boys, an adequate amount of body fat is important in the onset of their body fat. These alterations in amount of body fat indicate that 4.2 | Puberty in boys is initiated by the release of kisspeptin. As mentioned before, this activates the HPG axis, resulting in the release of GnRH from the hypothalamus, and consequently the release of LH and FSH 9,74 puberty. tosterone from the testes, to estrogen (Figure 3). of the development of secondary sex characteristics in boys. Additionally, leptin can affect fertility in men as it can modulate the nutritional support of spermatogenesis, and moreover, dysfunction of spermatogenesis is associated with an increased leptin level and 73 58 2,60-62 HPG axis from the pituitary gland (Figure 1). and LH stimulates the secretion of testosterone from the testes, which inhibits the release of kisspeptin from the KNDy neurons and 9,48 in men, the release of kisspeptin is more consistent, causing a con- 29,48 subsequently GnRH from the hypothalamus. receptors expressed on KNDy neurons. In humans, KNDy neurons Contrarily to women, LH-induced testosterone levels lead to the stant release of LH. development of secondary sex characteristics in boys. differences between sexes in kisspeptin release are related to a sex- specific and sex steroid-dependent kisspeptin system as estrogen and progesterone modulate kisspeptin activity through the sex-steroid 48 in the infundibular nucleus are involved in negative and positive sex- 48 tal exposure to sex steroids and result in sex-specific differences in steroid feedbacks. kisspeptin release. These sexual dimorphisms are induced by perina- 75,76 4.3 | Adipokines The association between obesity and puberty onset in boys is rather controversial compared with findings in girls. Most studies reported an early onset of puberty in boys associated with increased ate adipose tissue from actual breast tissue. stages are more difficult to assess than female stages as boys lack a more determined marker such as menarche. Thirdly, puberty onset can be indicated by the activation of the HPG axis, and the presence of these secondary sex characteristics is the result of hormonal 2 14,17,22,23,50,51,77,78 BMI, 20,49 all while others reported no associations at Current markers used 79 16,80 or a delayed onset of puberty (Table 1). The presence of excessive adipose tissue can be involved in puberty onset in boys as the secretion of adipokines can modulate both adrenarche and gonadarche. Leptin can affect adrenarche by modulating both the HPG and HPA axes,33 and moreover, androgen levels were positively 55 nal androgen secretion in boys with premature adrenarche was not associated with plasma leptin levels. Nevertheless, enhanced adre- 9 In more detail, 61,62 adiponectin, and individuals with obesity often have high levels of cir- Moreover, inflammatory cytokines, TNF-α, and IL-6, inhibit expression of the leptin receptor in the testis. FSH induces spermatogenesis, too. function and role still have to be examined. 64 High leptin and low adiponectin and fat tissue can convert testosterone Both processes might result in the delay 29,61,79 81,82 In men, other adipokines like chemerin are found in the gonads 65 Thus, particularly high leptin and low adiponectin levels stimulate the HPG axis and thereby accelerate the onset of puberty in boys. Additionally, leptin can dysregulate the development of secondary sex characteristics and spermatogenesis by affecting testosterone levels and nutritional sup- port of spermatogenesis. 5 | LIMITATIONS AND FUTURE RESEARCH DIRECTIONS Even though multiple epidemiological studies have shown the link between puberty onset and obesity, there are some important limita- tions. Firstly, determining both the onset and stage of puberty is rather difficult. For instance, assessing the stage of breast develop- ment in girls with obesity is complicated as clinicians should differenti- 2 changes in response to the activated HPG axis. to determine the onset of puberty refer to secondary sex characteris- tics, such as testicular volume in boys and breast development in girls. A more accurate measurement of puberty onset would be to combine secondary sex characteristics with plasma or serum hormone level measurements such as LH, FSH, adipokines, e.g. leptin. Thereby, differences in puberty measurements could explain variations in the age of puberty onset between boys and girls within different Thereby, resistin is expressed in the testes of rats, but its exact 83 Secondly, male pubertal 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License NIEUWENHUIS ET AL. 7 of 10 FIGURE 3 Adipokines affecting the initiation of puberty in boys. Leptin activates kisspeptin secretion in KNDy neurons, this activates the production of gonadotropin releasing hormone (GnRH) from the hypothalamus. GnRH stimulates the pituitary gland to secrete follicle stimulating hormone (FSH) and luteinising hormone (LH), activating the production of testosterone from the testes allowing the development of secondary sex characteristics. Leptin also inhibits the production of testosterone, which may cause a delayed onset of puberty. Adiponectin inhibits GnRH release. Low levels of adiponectin, as a result of TNF-α and IL-6 expression, lead to a reduced inhibition of GnRH. In response to GnRH release, the pituitary gland will secrete FSH and LH, and the testes will produce testosterone resulting in the development of secondary sex characteristics in boys countries, and In addition, the inclusion of a of puberty. ferent time points is complicated, as subjects examined several decades ago presented pronounced differences concerning lifestyle patterns such as nutrition and exercise habits. Lastly, obesity or over- weight is often determined by BMI, a classification based on weight and height measurements. Additionally, it is important that all studies studies or across continents, ethnicities proper age range (8-16 years) is important when assessing the onset (Figure 4). 12-15,17,20-23,49,77-79,84,85 30,47 Furthermore, comparison between studies from dif- 86 Specifically in children, BMI is often dependent on age and growth use the same anthropometric standards and sex-specific cut-offs. 13,14,16-23,49-51,77-80 fat and would represent a more accurate measurement in its regard. Based on this review, several suggestions can be made for further research. Firstly, the roles of adipokines like resistin, chemerin, visfatin, and omentin in puberty onset, fertility, and sexual maturation should be examined in detail. Secondly, future research examining the onset of puberty should combine indicators of puberty onset (e.g. breast development or testicular volume) with plasma or serum hor- mone measurements such as LH, FSH, sex-steroids, adipokines (e.g. spurts. ment in case of growth spurts. distribution of body fat should be taken into account in determining puberty and obesity in children. For instance, the body adiposity index (BAI), which was introduced in 2011 by Bergman et al.,87 uses hip cir- cumference and height in order to estimate the percentage of body 87 Thereby, BMI is a less accurate measure- F I G U R E 4 87,88 Therefore, both percentage and Average age of puberty onset in Europe, China, and the United States according to several studies from Table 1. Age of puberty onset ranges from 8.47 to 13.33 years in girls and from 8.63 leptin), and body fat distribution (e.g. BAI,87 waist-hip ratio's and/or dual-energy X-ray absorptiometry (DXA)2). Additionally, defining con- sistent and general measurements of puberty in both boys and girls, combined with a proper age range (8-16 years), would facilitate the comparisons between different studies and their results. 12-15, 17, 20-23, 25-29, 31 to 13.7 years in boys. included if average age of markers used to assess puberty was not reported. Pink: girls. Blue: boys Studies (Table 1) were not 39, 56 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 8 of 10 NIEUWENHUIS ET AL. 6 | CONCLUSION In conclusion, epidemiological data regarding obesity and puberty onset in girls show similar outcomes as adiposity results in the early onset of puberty in girls. The majority of the studies examining boys with obesity indicate an early onset of puberty, while not all reported an earlier onset of puberty. In detail, high leptin, TNF-α, and IL-6 levels combined with low adiponectin levels stimulate the activation of the HPG axis in girls and boys with obesity, and 5, 45, 50, 51 REFERENCES 1. Kumar S, Kelly AS. Review of childhood obesity: from epidemiology, etiology, and comorbidities to clinical assessment and treatment. May- o Clin Proc. 2017;92(2):251-265. 2. Reinehr T, Roth CL. Is there a causal relationship between obesity and puberty? The Lancet Child & adolescent health. 2019;3(1):44-54. 3. WorldHealthOrganization. Facts and figures on childhood obesity. 2017. 4. Guglielmi V, Sbraccia P. Obesity phenotypes: depot-differences in adipose tissue and their clinical implications. Eat Weight Disord. 2018; 23(1):3-14. 5. Gomez-Hernandez A, Beneit N, Diaz-Castroverde S. Escribano O. 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FUNDING INFORMATION This research was funded by Europees Fonds voor Regionale Ontwikkeling (EFRO), project BriteN 2016. ORCID Ilse A.C. Arnoldussen Amanda J. Kiliaan https://orcid.org/0000-0002-7395-5284 https://orcid.org/0000-0002-2158-6210 13, 14, 16-26, 29-32 Furthermore, several receptors Nevertheless, We conclude Search strategy We searched PubMed for articles published before Novem- ber 15th, 2019 using relevant keywords, including âonset of puberty and adiposity/obesityâ, âonset of pubertyâ, âchildren with obesityâ, âadipose tissueâ, âchildhood obesityâ, âadiposityâ, âobesityâ, âadipokine(s)â, âHPG axisâ, âadipokines ovary/ova- riesâ, or âadipokines testesâ, either alone or in combination. 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Obesity Reviews. 2020;21:e13005. https://doi.org/ 10.1111/obr.13005 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are gover
French I- Le Loup et les Sept Petites ChĂšvres
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