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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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Ann Epidemiol. 2017;27(3):187-93.e2. 16. Glass NA, Torner JC, Letuchy EM, et al. The relationship between greater prepubertal adiposity, subsequent age of maturation, and bone strength during adolescence. Journal of bone and mineral research: the official journal of the American Society for Bone and Min- eral Research. 2016;31(7):1455-1465. 17. Holmgren A, Niklasson A, Nierop AF, et al. Pubertal height gain is inversely related to peak BMI in childhood. Pediatr Res. 2017;81(3): 448-454. 18. Kaplowitz PB, Slora EJ, Wasserman RC, Pedlow SE, Herman- Giddens ME. Earlier onset of puberty in girls: relation to increased body mass index and race. Pediatrics. 2001;108(2):347-353. 19. Kelly Y, Zilanawala A, Sacker A, Hiatt R, Viner R. Early puberty in 11-year-old girls: Millennium Cohort Study findings. Arch Dis Child. 2017;102(3):232-237. 20. Lazzeri G, Tosti C, Pammolli A, et al. Overweight and lower age at menarche: evidence from the Italian HBSC cross-sectional survey. BMC Womens Health. 2018;18(1):168-174. thereby an early onset of obesity. leptin can inhibit the production of testosterone in boys and subse- quently inhibit the development of secondary sex characteristics affecting spermatogenesis. for other adipokines, like resistin and omentin, are present in the testes and ovaries suggesting a role in puberty or reproduction; 58, 71 however, their plausible function is still unknown. that adipokines may be key regulators in an early onset of puberty in both girls and boys with obesity, specifically by affecting the HPG axis during gonadarche. Future research should focus on assessing puberty onset by measuring consistent puberty markers and determine the percentage of body fat and its distribution and adipokines and hormone serum levels particularly involved in the HPG axis. CONFLICTS OF INTEREST The authors declare no conflict of interest. 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. Selection criteria used were English language, longitudinal or cross-sectional studies assessing the onset of puberty, including menarche, thelarche, spermarche, or voice break, combined with high BMI or obesity/adiposity, and articles assessing or reviewing adipokines and its effects on the reproductive system. 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. 9 of 10 21. Lian Q, Mao Y, Luo S, et al. Puberty timing associated with obesity and central obesity in Chinese Han girls. BMC Pediatr. 2019; 19(1):1-7. 22. Deng Y, Liang J, Zong Y, et al. Timing of spermarche and menarche among urban students in Guangzhou, China: trends from 2005 to 2012 and association with Obesity. Sci Rep. 2018;8(1):263-270. 23. Li W, Liu Q. Association of prepubertal obesity with pubertal devel- opment in Chinese girls and boys: a longitudinal study. 2018;30: e23195. 24. Mendle J, Beltz AM, Carter R, Dorn LD. Understanding puberty and its measurement: ideas for research in a new generation. Journal of research on adolescence: the official journal of the Society for Research on Adolescence. 2019;29(1):82-95. 25. Pagani S, Meazza C, Gertosio C, Bozzola E, Bozzola M. Growth hor- mone receptor gene expression in puberty. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2015;47:581-584. 26. Abreu AP, Kaiser UB. Pubertal development and regulation. Lancet Diabetes Endocrinol. 2016;4(3):254-264. 27. Aguirre RS, Eugster EA. Central precocious puberty: from genetics to treatment. Best Pract Res Clin Endocrinol Metab. 2018;32(4): 343-354. 28. Sultan C, Gaspari L, Maimoun L, Kalfa N, Paris F. Disorders of puberty. Best Pract Res Clin Obstet Gynaecol. 2018;48:62-89. 29. Skorupskaite K, George JT, Anderson RA. The kisspeptin-GnRH path- way in human reproductive health and disease. Hum Reprod Update. 2014;20(4):485-500. 30. Dahl SK, Amstalden M, Coolen L, Fitzgerald M, Lehman M. Dynorphin immunoreactive fibers contact GnRH neurons in the human hypothal- amus. Reprod Sci. 2009;16(8):781-787. 31. Navarro VM, Gottsch ML, Chavkin C, Okamura H, Clifton DK, Steiner RA. Regulation of gonadotropin-releasing hormone secretion by kisspeptin/dynorphin/neurokinin B neurons in the arcuate nucleus of the mouse. J Neurosci. 2009;29(38):11859-11866. 32. Zhai L, Liu J, Zhao J, et al. Association of obesity with onset of puberty and sex hormones in chinese girls: a 4-year longitudinal study. PLoS ONE. 2015;10(8):1-12, e0134656. 33. Cizza G, Dorn LD, Lotsikas A, Sereika S, Rotenstein D, Chrousos GP. Circulating plasma leptin and IGF-1 levels in girls with premature adrenarche: potential implications of a preliminary study. Horm Metab Res. 2001;33(3):138-143. 34. Cousminer DL, WidĂ©n E, Palmert MR. The genetics of pubertal timing in the general population: recent advances and evidence for sex-spec- ificity. Curr Opin Endocrinol Diabetes Obes. 2016;23(1):57-65. 35. Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child. 1969;44(235):291-303. 36. Lacroix AE, Whitten R. Physiology. Treasure Island (FL): Menarche. StatPearls. StatPearls Publishing; 2018. 37. McDowell MA, Brody DJ, Hughes JP. Has Age at Menarche Chan- ged? Results from the National Health and Nutrition Examination Sur- vey (NHANES) 1999â2004. J Adolesc Health. 2007;40(3):227-231. 38. de Muinich Keizer SM, Mul D. Trends in pubertal development in Europe. Hum Reprod Update. 2001;7(3):287-291. 39. Talma H, Schönbeck Y, van Dommelen P, Bakker B, van Buuren S, Hirasing RA. Trends in menarcheal age between 1955 and 2009 in the Netherlands. PLoS ONE. 2013;8:e60056-e60056. 40. Kaplan HS, Lancaster JB. An evolutionary and ecological analysis of human fertility, mating patterns, and parental investment. Off- spring: Human fertility behavior in biodemographic perspective. 2003;1: 170-223. 41. Mitan LA. Menstrual dysfunction in anorexia nervosa. J Pediatr Adolesc Gynecol. 2004;17(2):81-85. 42. Xu H, Li P-H, Barrow TM, et al. Obesity as an effect modifier of the association between menstrual abnormalities and hypertension in young adult women: Results from Project ELEFANT. PLoS ONE. 2018; 13(11):e0207929-e0207929. 43. Tauqeer Z, Gomez G, Stanford FC. Obesity in women: insights for the clinician. J Womens Health (Larchmt). 2018;27(4):444-457. 44. de Ridder CM, Thijssen JH, Bruning PF, Van den Brande JL, Zonderland ML, Erich WB. Body fat mass, body fat distribution, and pubertal development: a longitudinal study of physical and hormonal sexual maturation of girls. J Clin Endocrinol Metab. 1992;75(2): 442-446. 45. Lassek W, Gaulin S. Brief communication: menarche is related to fat distribution. Am J Phys Anthropol. 2007;133(4):1147-1151. 46. Loomba-Albrecht LA, Styne DM. Effect of puberty on body composi- tion. Curr Opin Endocrinol Diabetes Obes. 2009;16:10-15. 47. Simonneaux V, Bahougne T. A multi-oscillatory circadian system times female reproduction. Front Endocrinol. 2015;6:1-15. 48. Marques P, Skorupskaite K, George JT, Anderson RA. Physiology of GNRH and gonadotropin secretion. In: Feingold KR, Anawalt B, Boyce A, et al., eds. Endotext. Endotext.org: South Dartmouth (MA); 2000. 49. Barcellos Gemelli IF, Farias EDS, Souza OF. Age at menarche and its association with excess weight and body fat percentage in girls in the Southwestern Region of the Brazilian Amazon. J Pediatr Adolesc Gynecol. 2016;29(5):482-488. 50. Aksglaede L, Juul A, Olsen LW, Sorensen TI. Age at puberty and the emerging obesity epidemic. PLoS ONE. 2009;4:1-6, e8450. 51. Ribeiro J, Santos P, Duarte J, Mota J. Association between over- weight and early sexual maturation in Portuguese boys and girls. Ann Hum Biol. 2006;33(1):55-63. 52. Budak E, Fernandez Sanchez M, Bellver J, Cervero A, Simon C, Pellicer A. Interactions of the hormones leptin, ghrelin, adiponectin, resistin, and PYY3-36 with the reproductive system. Fertil Steril. 2006;85(6):1563-1581. 53. Castellano JM, Tena-Sempere M. Metabolic control of female puberty: potential therapeutic targets. Expert Opin Ther Targets. 2016; 20(10):1181-1193. 54. Venancio JC, Margatho LO, Rorato R, et al. Short-term high-fat diet increases leptin activation of CART neurons and advances puberty in female mice. Endocrinology. 2017;158(11):3929-3942. 55. l'Allemand D, Schmidt S, Rousson V, Brabant G, Gasser T, Gruters A. Associations between body mass, leptin, IGF-I and circulating adrenal androgens in children with obesity and premature adrenarche. Eur J Endocrinol. 2002;146(4):537-543. 56. Böttner A, Jr K, MĂŒller G, et al. Gender Differences of adiponectin levels develop during the progression of puberty and are related to serum androgen levels. J Clin Endocrinol Metabol. 2004;89(8):4053- 4061. 57. Unanue N, Bazaes R, Iñiguez G, Cortes F, Avila A, Mericq V. Adre- narche in Prader-Willi syndrome appears not related to insulin sensi- tivity and serum adiponectin. Horm Res. 2007;67(3):152-158. 58. Michalakis K, Mintziori G, Kaprara A, Tarlatzis BC, Goulis DG. The complex interaction between obesity, metabolic syndrome and repro- ductive axis: a narrative review. Metabolism: clinical and experimental. 2013;62(4):457-478. 59. Machinal-Quelin F, Dieudonne MN, Pecquery R, Leneveu MC, Giudicelli Y. Direct in vitro effects of androgens and estrogens on ob gene expression and leptin secretion in human adipose tissue. Endo- crine. 2002;18(2):179-184. 60. Dobrzyn K, Smolinska N, Kiezun M. Adiponectin: A new regulator of female reproductive system. Int J Endocrinol. 2018;2018:1-12, 7965071. 61. Martin LJ. Implications of adiponectin in linking metabolism to testic- ular function. Endocrine. 2014;46(1):16-28. 62. Mathew H, Castracane VD, Mantzoros C. Adipose tissue and repro- ductive health. Metabolism: clinical and experimental. 2018;86:18-32. 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 10 of 10 NIEUWENHUIS ET AL. 63. Sitticharoon C, Sukharomana M, Likitmaskul S, Churintaraphan M, Maikaew P. 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The usefulness of circulating levels of leptin, kisspeptin, and neurokinin B in obese girls with precocious puberty. 2018;34:627-630. 69. Lee J, Song J, Hootman JM, et al. Obesity and other modifiable fac- tors for physical inactivity measured by accelerometer in adults with knee osteoarthritis: data from the osteoarthritis initiative (OAI). Arthritis Care Res (Hoboken). 2012;53-61. 70. Bramswig J, Dubbers A. Disorders of pubertal development. Deutsches Arzteblatt international. 2009;106:295-303. quiz 04 71. Elias CF, Purohit D. Leptin signaling and circuits in puberty and fertil- ity. Cell Mol Life Sci. 2013;70(5):841-862. 72. Riumallo J, Durnin JV. Changes in body composition in adolescent boys. Eur J Clin Nutr. 1988;42(2):107-112. 73. Siervogel RM, Demerath EW, Schubert C, et al. Puberty and body composition. Horm Res. 2003;60(Suppl 1):36-45. 74. Zhang J. Gong M. Andrologia: Review of the role of leptin in the regu- lation of male reproductive function; 2018. 75. 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Secondary sexual characteristics in boys: data from the Pediatric Research in Office Settings Network. Pediatrics. 2012;130(5):e1058-e1068. 86. WHO. Physical status: the use and interpretation of anthropometry. Report of a WHO Expert Committee. World Health Organ Tech Rep Ser. 1995;854:1-452. 87. Akin I, Tolg R, Hochadel M, et al. No evidence of âobesity paradoxâ after treatment with drug-eluting stents in a routine clinical practice: results from the prospective multicenter German DES.DE (German Drug-Eluting Stent) Registry. JACC Cardiovasc Interv. 2012;5(2): 162-169. 88. Marcovecchio ML, Chiarelli F. Obesity and growth during childhood and puberty. World Rev Nutr Diet. 2013;106:135-141. How to cite this article: Nieuwenhuis D, Pujol-Gualdo N, Arnoldussen IAC, Kiliaan AJ. Adipokines: A gear shift in puberty. 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 goverDĂšs le dĂ©but de vos recherches, vous allez collecter, produire et exploiter des donnĂ©es. La gestion des donnĂ©es (Research Data Management - RDM) fait partie du processus de recherche. Elle concerne l'ensemble des opĂ©rations de collecte, description, stockage, traitement, analyse, archivage et mise en accĂšs des donnĂ©es. (extrait de : Passeport pour la Science Ouverte. Guide pratique pour les doctorants ) "La science ouverte est la diffusion sans entrave des publications et des donnĂ©es de la recherche. Elle sâappuie sur lâopportunitĂ© que reprĂ©sente la mutation numĂ©rique pour dĂ©velopper lâaccĂšs ouvert aux publications et â autant que possible â aux donnĂ©es de la recherche. "Les donnĂ©es de la recherche sont la matiĂšre premiĂšre de la connaissance. Les partager, c'est ouvrir de nouvelles perspectives scientifiques" Source : Plan national pour la Science ouverte - MinistĂšre ESR - Juillet 2018 Source image : https://bibliotheques.univ-tlse3.fr/file/composantes-science-ouverte Cette page est une introduction Ă la gestion des donnĂ©es de recherche. Elle prĂ©sente quelques concepts et Ă©tapes clĂ©s pour vous engager dans cette dĂ©marche. Consultez les liens pour approfondir vos connaissances. âą What are data ? DĂ©finition des donnĂ©es de recherche de lâOCDE (2007) « Enregistrements factuels (chiffres, textes, images, sons) utilisĂ©s comme source principale pour la recherche scientifique et gĂ©nĂ©ralement reconnus par la communautĂ© scientifique comme nĂ©cessaires pour valider les rĂ©sultats de la recherche. Un ensemble de donnĂ©es de recherche constitue une reprĂ©sentation systĂ©matique et partielle du sujet faisant lâobjet de la recherche ». Exemples âą les images dâune ville prĂ©historique deviennent des donnĂ©es pour un chercheur qui Ă©tudie lâhistoire de cette ville; âą les « donnĂ©es » dâun linguiste peuvent ĂȘtre des Ă©crits ou des discours, des enregistrements de locuteurs ; âą les « donnĂ©es » dâun mĂ©diĂ©viste sont des sources archivistiques, archĂ©ologiques, Ă©pigraphiques, iconographiques, littĂ©raires ; âą les « donnĂ©es » dâun gĂ©ologue rassemblent des coupes et observations de terrain consignĂ©es sur un carnet, des rĂ©sultats de carottage, des analyses dâĂ©chantillons, des donnĂ©es sismographiques⊠⹠⹠Pourquoi partager ses donnĂ©es ? "La science ouverte vise Ă construire un Ă©cosystĂšme dans lequel la science est plus cumulative, plus fortement Ă©tayĂ©e par des donnĂ©es, plus transparente, plus rapide et dâaccĂšs plus universel.La science ouverte favorise Ă©galement les avancĂ©es scientifiques, particuliĂšrement les avancĂ©es imprĂ©vues, ainsi que lâinnovation, les progrĂšs Ă©conomiques et sociaux, en France, dans les pays dĂ©veloppĂ©s et dans les pays en dĂ©veloppement. Enfin, la science ouverte constitue un levier pour lâintĂ©gritĂ© scientifique et favorise la confiance des citoyens dans la science. Elle constitue un progrĂšs scientifique et un progrĂšs de sociĂ©tĂ©." Source : Plan national pour la Science Ouverte (2018) Les enjeux de l'Open Data âą enjeux patrimoniaux o preuve et mĂ©moire (Ă©viter les pertes de donnĂ©es) âą enjeux Ă©conomiques o valeur Ă©conomique de la donnĂ©e o rĂ©utilisation gratuite ou payante des donnĂ©es, exploitation des rĂ©sultats de recherches antĂ©rieures (Ă©viter de refaire ce qui a dĂ©jĂ Ă©tĂ© validĂ©), o accĂ©lĂ©ration de l'innovation et le retour sur investissement dans la R&D âą enjeux scientifiques o de "hypothesis-driven" Ă "data-driven" o plus de visibilitĂ© pour le scientifique âą enjeux sociĂ©taux o participation des citoyens et de la sociĂ©tĂ© civile : "Citizen science" o confiance en la recherche Pour aller plus loin âą Site Doranum : https://doranum.fr/enjeux-benefices/fiche-synthetique/ âą Adopter de bonnes pratiques tout au long du cycle de vie des donnĂ©es De bonnes pratiques de gestion Ă toutes les Ă©tapes du cycle de vie de la donnĂ©e sont un prĂ©alable indispensable Ă lâouverture des donnĂ©es et Ă leur rĂ©utilisation. âą Rechercher des donnĂ©es Pour identifier des jeux de donnĂ©es (datasets) pertinents pour votre thĂšse, des outils de recherche sont disponibles. Suivez ces liens pour les dĂ©couvrir : âą Site Doranum : https://doranum.fr/acces-visualisation/rechercher-donnees/ âą Site DataCC - Vos besoins, trouver des donnĂ©es : https://www.datacc.org/vos-besoins/trouver-des-donnees/ âą Fiche CoopIST : Trouver des jeux de donnĂ©es via des bases pluridisciplinaires et des moteurs de recherche Pensez-aussi Ă consulter l'entrepĂŽt institutionnel Data INRAE Page de prĂ©sentation du portail âą Choisir les bons formats et bien organiser vos donnĂ©es ï§ Choisir des formats de fichier : https://www6.inrae.fr/datapartage/Gerer/Choisir-des-formats-de-fichier ï§ Nommer et organiser vos fichiers de donnĂ©es : https://www6.inrae.fr/datapartage/Gerer/Nommer-et-organiser-ses-fichiers-de-donnees Pour aller plus loin âą Jaouen, G.- GĂ©rer ses donnĂ©es. Pourquoi, Comment ? SĂ©minaire - Guadeloupe, du 25 au 27 Novembre 2019 â CRAG INRA âą Bien dĂ©crire et documenter ses donnĂ©es La description dâun jeu de donnĂ©es se fait Ă lâaide de mĂ©tadonnĂ©es (*) qui doivent apporter suffisamment d'Ă©lĂ©ments (sur la collecte des donnĂ©es, les unitĂ©s de mesure employĂ©es...) pour chercher et trouver le jeu de donnĂ©es, juger de sa qualitĂ©/fiabilitĂ©, et pouvoir le comprendre ou le rĂ©utiliser dans un autre contexte. (*) DĂ©finition des mĂ©tadonnĂ©es : Ensemble dâinformations structurĂ©es qui dĂ©crit, explicite, localise une ressource informationnelle, dans le but dâen faciliter la recherche, lâusage, et la gestion. Source : NISO. Understanding Metadata. 2004. Quelques liens utiles : âą Site Doranum : https://doranum.fr/metadonnees-standards-formats/ âą DataCC : https://www.datacc.org/vos-besoins/documenter-ses-donnees/metadonnees/ âą Site DataPartage INRAE : https://www6.inrae.fr/datapartage/Gerer/Documenter-les-donnees En complĂ©ment des mĂ©tadonnĂ©es, la rĂ©daction d'un fichier READ ME.txt est Ă©galement recommandĂ©e. âą Stocker, sĂ©curiser, prĂ©server ses donnĂ©es Bien diffĂ©rencier les notions de stockage et d'archivage. Anticiper pour dĂ©terminer les donnĂ©es Ă Ă©liminer et celles qui doivent ĂȘtre prĂ©servĂ©es Ă long terme. âą Dans l'environnement INRAE : https://www6.inrae.fr/datapartage/Gerer/Stocker-les-donnees âą Site Doranum : https://doranum.fr/stockage-archivage/ âą Site DataCC : https://www.datacc.org/vos-besoins/conserver-ses-donnees/ âą Partager, ne pas partager ses donnĂ©es ? Dans le cadre de la Science Ouverte, il y a de plus en plus d'incitations voire d'exigences pour rendre accessibles les donnĂ©es, en particulier les donnĂ©es liĂ©es aux publications : âą de l'Ă©dition scientifique : de plus en plus de revues adoptent une "data policy" (Ă consulter dans les instructions aux auteurs) et exigent des auteurs qu'ils fournissent les donnĂ©es associĂ©es aux publications, âą des organismes de financement (ANR, Commission EuropĂ©enne ...), âą des politiques nationale (Plan national pour la Science ouverte - MinistĂšre ESR - Juillet 2018) et institutionnelle. Mais attention, toutes les donnĂ©es ne sont pas partageables : assurez-vous que vos donnĂ©es sont bien diffusables au regard du droit et des conditions d'exercice de votre thĂšse et de son mode de financement (se reporter Ă votre contrat de thĂšse). Les donnĂ©es produites dans les organismes de recherche publics sont communicables Ă tous si elles n'entrent pas dans le cadre d'exceptions lĂ©gales (sĂ©curitĂ© dĂ©fense, sĂ©curitĂ© des populations, patrimoine scientifique et technique, donnĂ©es personnelles, donnĂ©es liĂ©es au secret, statistique, etc.) Liens utiles : âą sur le site Data Partage, la page Partager-Publier ou la page : "DonnĂ©es de la recherche : qui a les droits, qui doit partager ?" âą le site INRAE dĂ©diĂ© Ă la protection des donnĂ©es personnelles et l'application du RGPD (RĂšglement gĂ©nĂ©ral sur la protection des donnĂ©es) : https://intranet.inrae.fr/cil-dpo âą Valoriser ses donnĂ©es Voici les principales voies de diffusion âą ï§ Partager ses donnĂ©es en les dĂ©posant dans un entrepĂŽt ï§ Choisir un entrepĂŽt ï§ DĂ©poser dans Data INRAE ï§ Partager ses donnĂ©es comme matĂ©riel supplĂ©mentaire d'un article (Ă la demande de l'Ă©diteur) ï§ Publier un Data Paper (article de donnĂ©es) : la meilleure voie en terme de visibilitĂ© des donnĂ©es, et pour faciliter leur rĂ©utilisation. Pour aller plus loin âą Site Doranum o DĂ©pĂŽts et entrepĂŽts. Comment et oĂč dĂ©poser mes donnĂ©es ? o Data papers et Data journals. Comment publier mes donnĂ©es comme un article scientifique ? âą Site DataCC o Valoriser ses donnĂ©es âą Site CoopIST o DĂ©poser des donnĂ©es de recherche dans un entrepĂŽt o RĂ©diger et publier un data paper dans une revue scientifique A tĂ©lĂ©charger : SynthĂšse du processus de rĂ©daction d'un article avec des donnĂ©es associĂ©es âą Pourquoi ne pas rĂ©diger un plan de gestion de donnĂ©es (PGD) pour votre thĂšse ? La thĂšse peut ĂȘtre assimilĂ©e Ă un projet et certaines universitĂ©s au Royaume Uni, aux Pays-Bas et plus rĂ©cemment en France prĂ©conisent la rĂ©daction d'un plan de gestion associĂ© Ă la thĂšse. Le PGD (ou DMP = Data Management Plan) est un outil de planification qui peut vous aider Ă anticiper et bien gĂ©rer toutes les Ă©tapes du cycle de vie de vos donnĂ©es, Ă limiter les risques de perte ou corruption de donnĂ©es, Ă adopter de bonnes pratiques de gestion, pour in fine produire des donnĂ©es respectueuses des principes FAIR, adoptĂ©s aujourd'hui par l'ensemble des acteurs de la recherche. Il est dĂ©sormais exigĂ© par la plupart des financeurs de la recherche (Commission EuropĂ©enne et ANR ...) dans le cadre de projets financĂ©s. RĂ©diger un PGD pour votre thĂšse, peut ĂȘtre un bon exercice pour vous prĂ©parer Ă la future rĂ©daction de rĂ©ponses Ă des appels d'offre. Comment faire en pratique ? âą Site DataPartage : Pourquoi et comment rĂ©diger un plan de gestion de donnĂ©es ? âą Site Doranum : https://doranum.fr/plan-gestion-donnees-dmp/, La minute vidĂ©o PGD âą Site DataCC : https://www.datacc.org/bonnes-pratiques/adopter-un-plan-de-gestion-des-donnees/ âą Suivre une classe virtuelle INRAE : Open Class "RĂ©daction d'un PGD" âą Produire des donnĂ©es FAIR ! Favoriser la production de donnĂ©es FAIR (Findable - Accessible - Interoperable - Reusable) est aujourd'hui un objectif soutenu par l'ensemble des acteurs de la recherche. Source : https://open-science-training-handbook.gitbook.io/book/ Si vous suivez les conseils et recommandations de cette page, vous avez toutes les chances d'avoir produit des donnĂ©es de qualitĂ©. Si vous prĂ©fĂ©rez une version illustrĂ©e : "Pensez FAIR" - https://datapartage.inrae.fr/Gerer/Cycle-de-la-donnee Affiche cycle de vie des donnĂ©es rĂ©alisĂ©e dans le cadre des Missions QualiNous & RGPD, INRAE-ACT Vous pouvez tester le niveau de "Fairification" de vos donnĂ©es grĂące Ă ces outils : ï§ ARDC : https://ardc.edu.au/resources/working-with-data/fair-data/fair-self-assessment-tool âą D'autres ressources pour se former ou s'autoformer En interne INRAE âą Formation Ă la science ouverte OSCAR - Module "Gestion et partage des donnĂ©es" âą Le site "Gestion et partage des donnĂ©es" âą Des classes virtuelles d'environ 2h (Open Class) sont rĂ©guliĂšrement proposĂ©es sur : o la rĂ©daction des plans de gestion de donnĂ©es, o le dĂ©pĂŽt et la description d'un jeu de donnĂ©es dans Data INRAE, o la rĂ©daction et la publication de data papers, Sites externes âą Le site DORANUM (DonnĂ©es de la Recherche : Apprentissage NUMĂ©rique Ă la gestion et au partage) propose un dispositif de formation Ă distance intĂ©grant de nombreuses ressources dâauto-formation dĂ©clinĂ©es sur diffĂ©rents supports (textes, infographies, vidĂ©os) et sur 9 thĂ©matiques. o Parcours interactif sur la gestion des donnĂ©es de la recherche (2020) o âą Le site DataCC. Accompagnement Ă la gestion des donnĂ©es de recherche en physique et en chimie : https://www.datacc.org/ o Data Stories : https://www.datacc.org/reseau-datacc/data-stories/ o âą Le dossier "Open Access & Open Data" rĂ©alisĂ© par l'Ecole des Ponts - ParisTech âą âą The Open Science Training Handbook : https://www.ouvrirlascience.fr/the-open-science-training-handbook/L'article contracte 3 l'article contracte 1: Les verbes âfaireâ et âjouerâ au prĂ©sent de lâindicatif / Les articles contractĂ©s4 min Quâest-ce que la vente ? Lâhistoire de la vente remonte de trĂšs loin, du temps de la mythologie avec Mercure qui a Ă©tĂ© considĂ©rĂ© comme Ă©tant le dieu du commerce. Ainsi, la pratique existe dĂ©jĂ depuis plus de 6 000 ans. Les premiĂšres techniques de vente ont vu le jour vers 350 avec Aristote. Il faudra attendre plusieurs siĂšcles avant dâarriver Ă la mĂ©thode de vente telle que nous la dĂ©finissons aujourdâhui, avec le client placĂ© au centre du processus. Quelques dĂ©finitions de la vente Dans le cadre dâune vente, un vendeur cĂšde un produit ou un service Ă un acheteur en contrepartie dâune somme dâargent. Ce qui diffĂ©rencie la vente de la notion de troc ou dâĂ©change. Juridiquement parlant, lâarticle 1582 du Code civil dĂ©finit la vente comme Ă©tant « une convention par laquelle lâun sâoblige Ă livrer une chose, et lâautre Ă la payer ». Le contrat de vente peut ĂȘtre Ă©tabli par Ă©crit ou verbalement. Il peut alors sâagir dâune prestation ou dâun bien corporel. Toutefois, certains types de vente doivent suivre une rĂ©glementation particuliĂšre. Notamment la vente de fonds de commerce, la vente Ă crĂ©dit ou encore la vente Ă domicile. En dâautres termes, la vente dĂ©signe lâensemble des mĂ©thodes et des actions effectuĂ©es par un commercial, dont le but est de vendre quelque chose Ă une tierce personne. La vente est ainsi le rĂ©sultat dâun accord ou dâune nĂ©gociation entre le vendeur et lâacheteur. Que peut-on vendre ? La vente ne se limite pas seulement Ă un produit. Il est possible de fournir des services, des prestations, des formations et bien plus encore. Le domaine de la vente est trĂšs vaste. En effet, on peut amener une personne Ă acheter une vision ou un avis politique, la convaincre de choisir un projet plutĂŽt quâun autre et ce ne sont que des exemples parmi tant dâautres. Quelle diffĂ©rence y a-t-il entre la vente et le marketing ? On a tendance Ă confondre ces deux termes. Or, le marketing et la vente dĂ©signent deux disciplines diffĂ©rentes â bien que complĂ©mentaires â et ayant le mĂȘme but. Celui de gĂ©nĂ©rer des revenus pour amĂ©liorer le chiffre dâaffaires dâune entreprise. Ă ce titre, lâun ne va pas sans lâautre. Les activitĂ©s de marketing Le marketing se concentre davantage sur le marchĂ©. Autrement dit, le responsable marketing se focalisera plus sur les besoins des clients et des prospects et sur lâĂ©laboration dâune solution pour rĂ©pondre Ă leurs attentes. Ainsi, il fera en sorte que la vente ait lieu. Pour ce faire, il se chargera du matĂ©riel promotionnel allant des simples brochures Ă lâorganisation de salons. Le marketeur se voit ainsi attribuer deux missions. PremiĂšrement, prĂ©senter une proposition attrayante en se basant sur les besoins des consommateurs qui sont identifiĂ©s Ă lâavance. Et deuxiĂšmement, crĂ©er et entretenir une relation durable et de confiance avec eux. Les activitĂ©s de vente ou « sales » Lâagent marketing attire le client vers un produit ou une marque. Quand cela est fait, câest au vendeur de prendre le flambeau. Ce dernier prend contact avec la clientĂšle dans le but dâune acquisition par celle-ci. Le plus dur dans le travail du commerçant est de transformer les leads ou prospects en vĂ©ritables clients. La vente est la discipline qui conduit le prospect Ă lâacte dâachat. Pour ĂȘtre plus clair, le marketing vise Ă attirer le prospect dans la boutique tandis que la vente lâamĂšne Ă faire des achats pour quâil devienne un client. Quelles sont les diffĂ©rentes formes de vente ? Dans un cadre BtoB ou BtoC, on distingue de nombreuses formes de vente rĂ©gies ou non par une rĂ©glementation spĂ©cifique. Les ventes hors Ă©tablissement AppelĂ©es Ă©galement « contrats hors Ă©tablissement », les ventes hors Ă©tablissement ont lieu lorsque le contrat est rĂ©glĂ© en dehors de lâĂ©tablissement commercial. Le dĂ©marchage Ă domicile et le porte-Ă -porte en font partie. Toutefois, pour Ă©viter les abus qui sont de plus en plus frĂ©quents, des dispositions ont Ă©tĂ© prises pour protĂ©ger le consommateur. La vente en liquidation Ăgalement rĂ©glementĂ©e, la vente en liquidation est effectuĂ©e lorsquâun commerçant doit dĂ©stocker sa marchandise ou Ă©couler un assortiment de biens Ă cause dâune circonstance dĂ©terminĂ©e. Elle ne peut se faire que pendant deux mois tout au plus et doit sâaccompagner dâune publicitĂ© et dâune rĂ©duction de prix, parfois Ă perte. Elle est autorisĂ©e dans le cas oĂč le commerçant souhaiterait suspendre, arrĂȘter ou changer dâactivitĂ©. Les ventes en soldes Tous les semestres, les entreprises sont autorisĂ©es Ă vendre leurs produits Ă un prix trĂšs rĂ©duit. Les pĂ©riodes de soldes sont rĂ©glementĂ©es par le Livre VI du CDE (Code du droit Ă©conomique) affĂ©rent aux pratiques du marchĂ© et Ă la protection du consommateur. Elles se situent du 3 au 31 janvier inclus et du 1er au 31 juillet inclus. Comme pour le cas de la liquidation, il se peut que lâentreprise effectue une vente Ă perte. Le e-commerce ou le commerce Ă©lectronique La vente par Internet ou la vente en ligne est rĂ©gie par une rĂ©glementation relative au contrat et Ă la vente Ă distance. Lâentreprise conclut la vente par lâintermĂ©diaire de rĂ©seaux informatiques et, Ă ce titre, un paiement Ă©lectronique peut ĂȘtre nĂ©cessaire. En tant que commercialisation Ă distance, aucune prĂ©sence physique simultanĂ©e des deux parties nâest indispensable. Les ventes aux enchĂšres ou les ventes publiques Ă la diffĂ©rence des autres formes de vente, lâenchĂšre publique met en place une mĂ©thode de mise en concurrence transparente, car le bien est attribuĂ© au plus offrant. Lâorganisation dâune vente publique est aussi gĂ©rĂ©e par le Livre VI du CDE. Les rĂ©glementations concernant les contrats Ă distance ainsi que la vente hors Ă©tablissement peuvent ainsi ĂȘtre appliquĂ©es. Il existe des locaux spĂ©cialement destinĂ©s pour ce type de vente et seuls des biens usagĂ©s peuvent ĂȘtre mis en vente.L'articleL'article partitif