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Make a multiple choice quiz for my year 8 science students based on the science in this transcript from a video: 3°C 0:04 It can be the difference between snow and sleet 0:08 Wearing a jacket or not 0:11 In your day-to-day life, it may not seem significant 0:15 But 3°C of global warming would be catastrophic 0:20 Heatwaves, droughts, extreme precipitation, even fire 0:25 3°C of warming is really disastrous 0:28 The scary thing is, the world is well on its way there 0:32 Since the industrial revolution, the Earth has warmed between 1.1°C and 1.3°C 0:40 This is a problem that babies you pass in the street will have to live with 0:46 Children born today... 0:47 ...are up to seven times more likely to face extreme weather than their grandparents 0:52 If global temperatures do rise by 3°C... 0:55 ...what would their world look like? Climate change is already having devastating effects 1:03 Rising sea levels 1:05 Desertification 1:07 Hollywood has always enjoyed imagining the end of the world 1:11 While blockbusters like this are clearly fiction... 1:14 ...this film will show the scenario we all face... 1:17 ...unless more drastic measures are taken to stop burning fossil fuels 1:30 In some parts of the world the effects of inaction are already clear 1:35 The slums of Bangladesh’s capital are filling up with climate migrants 1:41 Minara comes from Bhola District, an area in southern Bangladesh 1:46 There, like many other parts of the country... 1:49 ...rivers swollen by heavier rain and melting Himalayan glaciers... 1:53 ...are washing away people’s homes 1:56 Many, like her, have lost everything 2:00 Our home in Bhola had endless amounts of land 2:03 There was lots of space for farming, we had a spacious house 2:08 There were different types of fruits, vegetation and trees growing at home 2:12 We used to eat the fruit from our own trees 2:18 I can’t eat them now because they don't exist anymore 2:21 Since the river flooded for the third time, I had to flee to Dhaka 2:26 Life was much better back home 2:29 It was unbearable to live through, truly intolerable 2:33 We didn’t have the time to save anything at all 2:38 1.1°C to 1.3°C of global warming has already transformed Minara’s life 2:45 It’s one of the reasons why so many migrants like her... 2:47 ...are moving to the city each year... 2:50 ...nearly 400,000 according to the last estimate 2:53 And climate models show there could be much worse to come How climate modelling works 3:02 Climate scientist Joeri Rogelj... 3:04 ...has spent the last ten years modelling future climate scenarios... 3:08 ...for the United Nations 3:10 The models we use to carry out this exercise... 3:13 ...really represent the state of the art... 3:15 ...of our current knowledge of climate change and where we are heading 3:19 Joeri’s projections use data collected by hundreds of scientists around the world 3:26 Here this is the 3°C level... 3:28 ...and so there is at least a one-in-four chance that under current policies... 3:32 ...we would hit 3°C by the end of the century 3:36 This is just one of the scenarios Joeri looks at 3:40 Another one imagines that all policy promises are kept 3:44 The most optimistic assumes that all promises have been kept... 3:47 ...and net-zero targets are met 3:50 Where our best estimate ends up around 2°C at the end of the century... 3:54 ...there is still a one-in-20 chance that we end up with 3°C instead 3:59 One would not be entering a plane if there is a one-in-20 chance... 4:03 ...that the plane will crash Nowhere is safe from global warming 4:07 A rise of 3°C would affect everyone 4:10 Even wealthy cities in rich countries wouldn’t be immune to the consequences 4:15 European capitals like Paris and Berlin... 4:18 ...would bake under more extreme heatwaves 4:22 Frequent storm-surges in New York could turn parts of the city desolate 4:27 In many ways, cities magnify, intensify climate events 4:33 Cities are hotter than the places around them... 4:36 ...they tend to be more vulnerable to flooding 4:39 And you can get a really bad event in a city in a way that you can’t in the countryside 4:46 And because of their denser populations... 4:49 ...disasters in a city affect far more people 4:52 Some cities might be badly prepared for the changes coming 4:56 But they have the means to adapt 4:59 Cities tend to be wealthier than surrounding places 5:03 They have a lot of amenities 5:05 A city that has taken seriously the risks of a 3°C world... 5:08 …wouldn’t necessarily be a worse place to be in a 3°C world 5:12 But a city that hasn’t prepared for these sort of eventualities... 5:16 ...that might be a really nasty place The impact of prolonged droughts 5:20 So far, many developed cities have got off lightly... 5:24 ...but some rural parts of the world are suffering disproportionately 5:29 Smallholders—small-scale farmers—are particularly vulnerable to climate change 5:35 And there are over 600 million around the world 5:38 Smallholders with farms under two hectares... 5:40 ...produce around a third of the global food supply 5:46 Central America’s “Dry Corridor”... 5:48 ...supports a mix of smallholdings and medium-sized farms 5:53 Sandwiched between the Pacific Ocean and the Caribbean Sea... 5:56 ...the area is prone to droughts 6:08 Israel Ramírez Rivera is a smallholder in Guatemala 6:12 Here, climate change is making the dry seasons longer, and more severe 6:18 This is the biggest ear of maize that this plot could deliver 6:23 He depends on his crops of corn and beans 6:26 But they’re getting harder to grow 6:30 The surrounding mountains... 6:32 ...used to provide us with native food... 6:38 ...and now that isn’t an option anymore... 6:41 ...due to climate change and its effects 6:46 Nearly two-thirds of the smallholders in the Dry Corridor now live in poverty 6:52 The impact of all of this for us... 6:59 ...malnutrition among children 7:03 We’ve lost a few 7:07 For my crops especially, the midsummer heat is harder than before 7:16 The plant dries up and can’t provide us... 7:19 ...with the necessary food provision 7:24 Severe droughts in Central America... 7:26 ...are now four times more likely than they were last century 7:30 Many families from here have gone to the States 7:37 The economic despair and debts... 7:44 ...have pushed many people from this community to do this journey 7:53 Migration from Guatemala to the United States has quadrupled since 1990 7:59 Not all of this has been due to climate change 8:02 But longer droughts would force even more to move 8:05 In a 3°C world, annual rainfall in this region... 8:09 ...could drop by up to 14% 8:12 At 3°C, over a quarter of the world’s population... 8:16 ...could endure extreme droughts for at least a month of the year 8:19 Northern Africa could see droughts that last for years at a time Rising sea levels, storm surges and flooding 8:24 But for some, too much water will be the problem 8:29 10% of the world’s population lives on a coastline... 8:32 ...that’s less than 10 metres above sea level 8:35 For these coastal inhabitants, a 3°C world would spell disaster 8:40 By 2100, global sea levels could have climbed by half a metre from 2005 levels 8:46 Low-lying cities like Lagos would be especially vulnerable... 8:49 ...with up to up to a third of the population displaced 8:54 And in Fiji, rising waters are already upending lives 9:04 You can see the graveyard there, it’s all under water now... 9:08 ...due to this rising sea level and climate change 9:15 The village of Togoru in Fiji is being swallowed by the sea 9:19 Barney Dunn, the village headman, has seen over half the village disappear 9:24 Relatives’ houses have been abandoned, and family graves are now under water 9:29 We have been asked by the government to relocate... 9:32 ...but no one wants to relocate... 9:34 ...because we have our great-great-grandparents down there in the sea 9:39 This is the place we’ve been brought up in 9:41 ...it’s not easy to leave 9:44 Past attempts to build a seawall haven’t worked 9:48 But Barney sees building a new one as the village’s only hope 9:52 If they do that, maybe we can save whatever is left 9:56 But if we don’t have the seawall, then it will be keep eroding and time will come... 10:01 ...maybe in ten,15 years, Togoru will be all eroded 10:05 Rising seas also mean storms cause more floods 10:11 And many more countries could suffer 10:14 The Philippines and Myanmar are just two countries... 10:17 ...that will also see an increase in storm surges in a 3°C world 10:21 To escape, many will move… 10:24 …often, to urban areas Extreme heat and wet-bulb temperatures 10:27 Half the world’s population already lives in cities... 10:31 ...almost a third in slums 10:36 For them, a 3°C world could be deadly 10:40 Minara has moved to Dhaka to escape the impact of climate change 10:44 But life could get even worse for her 10:47 I’m struggling a lot nowadays 10:49 The heat during the day is unbearable 10:52 Even late at night it doesn’t cool down 10:57 The heat is getting more intense every day 10:59 I mean, it’s going to get much worse 11:03 I can barely survive it now, how will I live through it in the future? 11:08 Dhaka is getting hotter 11:11 In the last 20 years the average daytime temperature... 11:13 ...has crept up by nearly half a degree 11:17 Days that approach 40°C are now being reported 11:20 And high so-called wet-bulb temperatures are on the rise 11:26 A wet-bulb temperature is a measure of heat and humidity 11:30 Humans cool themselves by sweating… 11:32 But in these conditions, when relative humidity is near 100%... 11:36 ...sweat doesn’t evaporate well 11:38 So people can’t cool down… 11:41 ...even if given unlimited shade and water 11:45 At a high wet-bulb temperature, the body can’t lose heat... 11:49 ...and so it gets hotter and hotter... 11:51 ...and the body is designed to work at a given temperature 11:53 And if it gets too hot inside, you will die 11:58 The human limit for wet-bulb temperatures is 35°C... 12:02 ...around skin temperature 12:04 Dhaka will have a much higher chance... 12:05 ...of reaching dangerous wet-bulb temperatures... 12:07 ...if global warming reaches 3°C 12:12 You can’t really adapt to that 12:14 You have to get out. If the temperature is so high that you can’t work... 12:20 ...can’t do hard manual labour outside for significant parts of the year... 12:25 ...then many places will become functionally no longer part of the economy 12:33 Jacobabad in Pakistan, and Ras al Khaimah, in the United Arab Emirates... 12:37 ...have already recorded deadly wet-bulb temperatures 12:40 More of the tropics and the Persian Gulf... 12:43 ...as well as parts of Mexico and the south-eastern United States... 12:47 ...could all get to this threshold by the end of the century 12:50 Climate modelling might show us the weather Increased migration and conflict 12:52 But it doesn’t show us its other effects on society 12:56 Established migration patterns could change 12:59 Climate disasters may exacerbate reasons people cross borders 13:03 Within countries, more people will move to cities 13:07 In a 3°C world, tens of millions of people a year... 13:10 ...could be displaced by disasters made worse by climate change 13:15 When people are displaced by climate... 13:18 …they may well go to cities... 13:19 ...because cities are the places that attract people from the countryside already 13:25 A lot of people who can get to the developed world... 13:28 ...not least because the developed world tends to be less hot, will give that a go 13:35 As migration around the world increases... 13:38 ...there could be more competition for fewer resources 13:42 Water—already a highly contested resource—will be a focal point 13:47 Turkey’s new Ilisu dam has reduced the flow of water into Iraq 13:53 China lays claim to rivers vital to India and Pakistan 13:57 The prospect of a water-conflict makes people very uneasy 14:03 How national tensions would exacerbate those sorts of reactions... 14:08 ...in a 3°C world... 14:09 ...is the sort of thing that no one should really want to find out 14:14 I think you’d have to be incredibly sanguine... 14:16 ...not to think that the sort of climate extremes that we talk about... 14:19 ...in a 3°C world wouldn’t lead some places... 14:22 ...to the brink of societal collapse 14:25 Those lucky enough to escape unrest... Adaptation and mitigation are crucial 14:28 ...would still have to adapt to a radically different world 14:32 People can adapt to climate change in all sorts of ways, one of the most obvious ones... 14:37 ...is air conditioning 14:39 But other ways to adapt at a local or regional level... 14:42 ...I mean, one of the most obvious is diversifying agriculture 14:47 There are physical things you can do, like seawalls 14:52 The fact that people can adapt and that adaptation will reduce suffering... 14:57 ...doesn’t mean that it will eliminate suffering 15:00 Suffering is built into this whole process of heating up the planet 15:06 Adaptation will only get the world so far 15:09 The best way to deal with a 3°C world... 15:12 ...is not to go to a 3°C world 15:14 And that’s why increasing efforts on mitigation are important 15:17 It’s why working towards negative emissions... 15:20 ...that could bring down the temperature after it peaks are important 15:25 Once you get to a 3°C world, you are in real bad global trouble 15:33 The scale of change needed... 15:35 ...and the slow progress of governments so far... 15:38 ...means 3°C of warming is uncomfortably likely unless more is done 15:44 Despite existing pledges, greenhouse-gas emissions... 15:48 ...are still set to rise by 16% from 2010 levels by 2030 15:54 The need to act has never been clearer 15:57 There’s still time to reduce emissions, so that a 3°C world remains fiction... 16:02 ...rather than becoming factOf the 7 billion people on Earth roughly 0:02 6 billion own a cell phone which is 0:05 pretty shocking given that only 4 and2 0:07 billion have access to a working toilet 0:09 so how are these popular gadgets 0:11 changing your body and brain If you're 0:13 looking down at your phone right now 0:15 your spine angle is equivalent to that 0:17 of an 8-year-old child sitting on your 0:19 neck which is fairly significant 0:21 considering people spend an average of 0:23 4.7 hours a day looking at their phone 0:26 this combined with the length of time 0:28 spent in front of computers has led to 0:30 an increase in the prevalence of myopia 0:32 or nearsightedness in North America in 0:34 the 1970s about one quar of the 0:36 population had myopia where today nearly 0:39 half do and in some parts of Asia 80 to 0:41 90% of the population is now nearsighted 0:44 and it can be hard to put your phone 0:46 down take for example the game Candy 0:48 Crush as you play the game you achieve 0:50 small goals causing your brain to be 0:52 rewarded with little bursts of dopamine 0:54 and eventually you're rewarded in the 0:56 game with new content this novelty also 0:58 gives little bursts of dopamine and 1:00 together create what is known as a 1:01 compulsion Loop which just happens to be 1:04 the same Loop responsible for the 1:05 behaviors associated with nicotine or 1:07 cocaine our brains are hardwired to make 1:10 us novelty seeking and this is why apps 1:12 on our phones are designed to constantly 1:14 provide us with new content making them 1:16 hard to put down as a result 93% of 1:19 young people aged 18 to 29 report using 1:21 their smartphone as a tool to avoid 1:23 boredom as opposed to other activities 1:26 like reading a book or engaging with 1:27 people around them this has created a 1:29 new term nomophobia the fear or anxiety 1:32 of being without your phone we also see 1:35 a change in brain patterns Alpha rhythms 1:37 are commonly associated with wakeful 1:39 relaxation like when your mind wanders 1:41 off whereas gamma waves are associated 1:44 with conscious attentiveness and 1:46 experiments have shown that when a cell 1:47 phone is transmitting say during a phone 1:49 call the power of these Alpha Waves is 1:52 significantly boosted meaning phone 1:54 Transmissions can literally change the 1:56 way your brain functions your smartphone 1:58 can also disrupt your sleep the screen 2:00 emits a blue light which has been shown 2:02 to alter our circadian rhythms 2:03 diminishing the time spent in deep Sleep 2:06 which is linked to the development of 2:07 diabetes cancer and obesity Studies have 2:10 shown that people who read on their 2:11 smartphone at night have a harder time 2:13 falling asleep and produce less 2:15 melatonin a hormone responsible for the 2:17 regulation of sleep wake Cycles Harvard 2:20 medical school advises the last 2 to 3 2:22 hours before bed be technology free so 2:24 pick up a book before bed instead of 2:26 course smartphones also completely 2:28 change our ability to access information 2:30 most notably in poor and minority 2:32 populations 7% of Americans are entirely 2:35 dependent on smartphones for their 2:37 access to the internet a 2014 study 2:40 found that the majority of smartphone 2:41 owners use their phone for online 2:43 banking to look up medical information 2:45 and searching for jobs so while phones 2:47 are in no way exclusively bad and have 2:50 been part of a positive change in the 2:51 world there's no denying that they are 2:53 changing us but many successful people 2:56 have now decided to take smartphone 2:58 vacations in order to increase 3:00 productivity in our new ASAP thought 3:01 video we break down the top six reasons 3:04 you should take a smartphone vacation 3:06 and how it could benefit your life right 3:08 now and subscribe for more weekly 3:09 science videos0:01 i pasticciotti presentano Federico II di 0:05 Sveia 0:07 Nel 0:09 1186 Costanza D'Alta Villa figlia del re 0:12 normno di Sicilia Ruggero II sposò ormai 0:16 trentenne Enrico VI di Svevia figlio 0:20 dell'imperatore Federico Barbarossa che 0:23 si servì di questo matrimonio per 0:26 stringere un'alleanza politica con la 0:28 monarchia siciliana 0:31 Purtroppo non fu un'unione felice sia 0:34 perché il marito aveva 10 anni in meno 0:37 della moglie sia perché lui non aveva un 0:40 bel carattere e pare che rinfacciasse 0:44 continuamente a costanza la sua età 0:47 avanzata temendo che ciò fosse causa di 0:50 sterilità 0:52 Alla morte di Federico Barbarossa nel 0:56 1190 Enrico VI ereditò dal padre il 1:00 titolo di imperatore del Sacro Romano 1:02 Impero ma era incapace di esercitare un 1:06 buon governo nei confronti dei sudditi 1:09 normanni che vivevano nel regno di 1:11 Sicilia portatogli in dote dalla moglie 1:14 Costanza 1:16 Così nel 1:18 1994 Enrico partì per una spedizione in 1:22 Sicilia senza la moglie al seguito e 1:25 fece in modo di essere incoronato re di 1:28 Sicilia il giorno di Natale nella 1:31 cattedrale di 1:33 Palermo Lo stesso giorno Costanza che 1:36 era in avanzato stato di gravidanza e 1:39 stava viaggiando in direzione di Palermo 1:42 per raggiungere il marito si rese conto 1:44 di essere prossima al 1:47 parto Se oggi nessuno più si meraviglia 1:50 della gravidanza di una quarantenne nel 1:52 Medioevo una gestazione a quell'età 1:55 sembrava una cosa praticamente 1:57 impossibile Pertanto si erano alimentate 2:01 voci malevoli sulla vera condizione di 2:04 costanza e neppure il marito pareva 2:07 realmente convinto della gravidanza 2:09 della moglie E dato che Costanza prima 2:12 di sposarsi era stata per un periodo in 2:16 monastero circolava addirittura la voce 2:19 che nel suo grembo ci fosse 2:21 l'anticristo che secondo una leggenda 2:24 medievale sarebbe nato dall'unione di 2:26 una vecchia monaca con un 2:29 frate Così Costanza decise di fermarsi 2:33 nella cittadina di Iesi e per fugare 2:36 ogni dubbio sulla sua gravidanza fece 2:39 allestire una tenda nella piazza 2:42 centrale della cittadina 2:44 marchigiana in modo da partorire al 2:47 cospetto di tutte le donne sposate del 2:50 paese Alcuni riferirono che il giorno 2:53 successivo al parto la regina lattò 2:56 pubblicamente il piccolo che poi fu 2:59 battezzato nella cattedrale di San 3:01 Ruffino di Assisi con il nome di 3:04 Federico 3:06 Ruggero Federico per indicare la 3:09 discendenza sveva quale nipote di 3:12 Federico 3:13 Barbarossa e Ruggero per sottolineare la 3:17 discendenza normanna dal primo re di 3:20 Sicilia Ruggero 3:23 d'Altavilla A soli 3 anni il piccolo 3:26 Federico rimase orfano e fu posto sotto 3:30 la tutela di Papa Innocenzo II da cui si 3:33 affrancò a 14 anni quando divenne prima 3:37 re di Sicilia e poi re di 3:41 Germania acquisendo il nome di Federico 3:44 II congiuntamente al titolo di 3:47 imperatore nel 1220 3:50 Ma Federico era più interessato 3:53 all'Italia che alla 3:54 Germania Così stabilì la sua corte in 3:57 Sicilia a 4:00 Palermo Federico II organizzò un regno 4:04 forte e 4:05 accentrato costruendo in tutta l'Italia 4:08 meridionale vari castelli dove collocò 4:11 le sue truppe che dovevano controllare 4:14 il territorio e sedare eventuali rivolte 4:18 Vanno menzionati in particolare il 4:21 castello di Melfi in Basilicata dove 4:25 furono promulgate le famose costituzioni 4:29 melfitane una raccolta di leggi scritte 4:32 rivolte a tutti gli abitanti del regno 4:35 con cui si limitavano i poteri dei 4:38 baroni locali e si vietava il ricorso 4:41 alla vendetta personale per affidarsi 4:44 invece alla giustizia stabilita dalle 4:47 leggi 4:48 C'era poi il castello di Trani che aveva 4:51 la funzione di sorvegliare l'ingresso 4:54 alla città e al porto E infine il 4:58 celeberrimo castel del Monte 5:01 caratterizzato da un'originale pianta 5:03 ottagonale attorniata da torri anch'esse 5:07 ottagonali che fungeva da dimora come 5:10 testimoniato dalla presenza di grandi 5:13 camini Uomo colto fine giurista 5:17 Amante dell'arte della letteratura 5:20 Federico II ospitò alla sua corte 5:22 studiosi e artisti provenienti da tutta 5:25 Europa Dialogò con intellettuali arabi e 5:29 fondò l'Università di Napoli che ancora 5:32 oggi porta il suo 5:35 nome Con l'editto di Salerno regolamentò 5:38 per la prima volta la professione del 5:41 farmacista separandola di fatto da 5:44 quella del medico scrisse anche un libro 5:48 un manuale sulla falconeria e sull'arte 5:52 venatoria chiamato de Arte venandi cum 5:57 avibus ossia l'arte di cacciare con gli 6:01 uccelli che fu uno dei primi manoscritti 6:04 con disegni a tema 6:08 naturalistico In una nota alla sua morte 6:11 il monaco Matteo Paris lo chiamerà 6:14 stupor Mundi cioè stupore del mondo Un 6:19 appellativo che racchiude l'essenza 6:21 della sua inestinguibile curiosità 6:25 intellettuale che lo portò ad 6:27 approfondire la filosofia l'astrologia 6:30 la matematica l'algebra la medicina e le 6:34 scienze naturali ha al punto da 6:37 impiantare a Palermo persino uno zoo 6:40 famoso ai suoi tempi per il gran numero 6:43 di animali esotici che conteneva anche 6:46 un 6:47 elefante I rapporti col papo però non 6:51 furono idiaci 6:53 Sia Papa Onorio II che Gregorio Io detto 6:57 anche il Papa Guerriero lo costrinsero a 7:00 intraprendere una nuova crociata in 7:02 Terra Santa minacciando di scomunicarlo 7:06 qualora non l'avesse 7:08 fatto Così dopo tanta insistenza da 7:11 parte del papato Federico si mise in 7:13 viaggio per la Terra Santa 7:16 Giunto in Oriente però non mosse guerra 7:19 ai musulmani ma preferì stringere 7:22 accordi con il sultano d'Egitto 7:25 ottenendo il controllo della città di 7:27 Gerusalemme e una tregua di 10 anni 7:32 Si trattava di conquiste importanti dal 7:34 punto di vista diplomatico ma al suo 7:37 ritorno Federico II fu accusato 7:40 duramente di essere sceso a patti con 7:42 gli 7:43 infedeli Nel suo programma di governo 7:47 Federico II era intenzionato a 7:49 riaffermare la sua autorità sui comuni 7:52 del Nord Italia fatto che preoccupava il 7:56 Papa il quale temeva il rafforzamento 7:59 del potere imperiale anche a nord dello 8:02 Stato Pontificio già confinante a sud 8:05 con il Regno di Sicilia 8:08 In pratica il Papa si sentiva 8:11 schiacciato sia a nord che a sud 8:14 dall'imperatore Così Papa Gregorio Io 8:18 appoggiò alcuni comuni che si riunirono 8:20 nella Lega Lombarda e che furono detti 8:24 guelfi A questi si contrapposero i 8:27 comuni ghibellini che decisero di 8:30 schierarsi a sostegno 8:33 dell'imperatore Iniziò così una 8:35 lunghissima contesa che avrebbe 8:38 dilaniato le città 8:41 italiane Tutto 8:43 chiaro ciao e al prossimo 8:49 video Se questo video ti è piaciuto ti 8:52 chiedo di fare mi piace cliccando 8:53 sull'icona qui sotto Per me è molto 8:55 importante quindi grazie in anticipo se 8:57 lo farai Per essere informato ogni volta 8:59 che pubblico un nuovo video ricorda di 9:01 cliccare anche sul grande pulsante rosso 9:02 Iscriviti e sulla campanella di fianco 9:05 [Musica] 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 Desirée Nieuwenhuis | Natàlia 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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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 ‘onset of puberty and adiposity/obesity’, ‘onset of puberty’, ‘children with obesity’, ‘adipose tissue’, ‘childhood obesity’, ‘adiposity’, ‘obesity’, ‘adipokine(s)’, ‘HPG axis’, ‘adipokines ovary/ova- ries’, or ‘adipokines testes’, 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. 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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, Müller 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. 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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 gover7th Science Quiz 40GR 10 Q4 SCIENCE 1-4040 Kenji SCIENCE Lymphatic SystemWHAT IS SCIENCE? - is a way in which answers related to NATURAL events are proposed. - a way in which people can learn and UNDERSTAND events in the NATURAL WORLD - based on OBSERVABLE EVENTS - a study of the NATURAL WORLD - a method of DISCOVERY and UNDERSTANDING by using a PROBLEM-SOLVING process called the?? - A systematic body of knowledge based on observation and experimentation. FOUR COMMON CHARACTERISTICS OF SCIENCE: 1. It focuses on the NATURAL WORLD. 2. Goes through experiment. 3. Relies on evidence. 4. Passes through the scientific community. WHAT IS TECHNOLOGY? Brian Arthur (2009) defined technology as: 1. a means to fulfill a human purpose 2. assemblage of practices and components 3. a collection of devices and engineering practices available to a culture. SOCIETY ST (Science Technology) would not exist without society. WHAT IS STS? Science and Technology and Society (STS) is the study of how society, politics and culture affect scientific research and technological innovation and how these, in turn affects society, politics and culture. EVENTS IN THE HISTORY OF SCIENCE AND TECHNOLOGY THAT TRANSFORMED THE SOCIETY (IN THE WORLD) ANCIENT PERIOD 3500 BC. - 500 AD EUROPE - use of fire by Homo Erectus CA 750,000 - Stone Headed Spears CA 45,000 - Wooden bow and arrow CA 20,000 - The Minoans build palaces in Crete CA 2,000 THE AMERICAS - The Folsom people living on eastern side of the Rocky Mountain developed sophisticated tools CA 8,000. - Pottery is made in South America CA 6,000 - Olmec sculpture carves figurines and giant human heads. CA 1200 ASIA AND OCEANA - Earliest known clay pots are made in Japan CA 11,000. - Bronze is first made in Thailand CA 4000 - A lunar calendar is developed in China CA 2950 - Chinese doctors begin using acupuncture CA 2500 - The Hindu calendar of 360 days was introduced in India CA 1000 AFRICA AND MIDDLE EAST - Homo erectus uses stone tools CA 1000000 - CA 15000 in Africa, bone harpoons are used for fishing. - Clay tokens are used for record keeping in Mesopotamia CA 7500 - Mesopotamian mathematicians discover the Pythagorean Theorem MEDIEVAL PERIOD CA 500 -1500 - Dark ages because few written records and evidences remained - Scholastic tradition was established by Charlemagne - Vertical windmills, spectacles, mechanical clock, water mills, gothic style were invented - Johannes Gutenberg invented the printing press RENAISSANCE PERIOD 14TH – 17TH CENTURY - Rebirth of revival - Printing with movable type allowed Bible, secular books made in large amount - Nicolas Copernicus presented a heliocentric theory - Galileo Galilei invented telescope INDUSTRIAL REVOLUTION 18TH CENTURY - Skilled workers were set aside because of the machines - Iron production, steam engine and textile flourished - Scottish James Watt improved steam engine Robert Fulton (steam boat) - The following were invented: Light bulb, telephone, first steam powered locomotive 19TH CENTURY - Age of machine and tools - Herman Helmholtz (law of conservation of energy) - James Clark Maxwell (light as electro-magnetic wave) - Henry Becquerel (radioactivity) - Marie and Pierre Curie (radium) - Hans Christian Oersted (electric current near the magnet) - Michael Faraday (magnet produces electricity) - Atomic Theory proposed by John Dalton - Electron discovered by JJ. Thomson - Telegraph developed by Samuel Morse 20TH CENTURY - Communication, transportation, military research were developed - Personal computer was created - Intel developed microprocessor - Apple was introduced by Steve Jobs and Steve Wozniak - Internet was created (ARPANET) - Henry Ford's mass production of cars - Artificial Intelligence was invented SCIENCE, TECHNOLOGY AND SOCIETY (PHILIPPINE HISTORY) Stone Age - Archeological findings show that modern man from Asian mainland first came over land on across narrow channels to live in Batangas and Palawan about 48,000 B.C. - Subsequently they formed settlement in Sulu, Davao, Zamboanga, Samar, Negros, Batangas, Laguna, Rizal, Bulacan and Cagayan. Inventions - They made simple tools and weapons of stone flakes and later developed method of sawing and polishing stones around 40,000 B.C. - By around 3,000 B.C. they were producing adzes ornaments of seashells and pottery. Pottery flourished for the next 2,000 years until they imported Chinese porcelain. Soon they learned to produce copper, bronze, iron, and gold metal tools and ornaments. Iron Age - The Iron Age lasted from the third century B.C. to 11th century A.D. During this period Filipinos were engaged in extraction smelting and refining of iron from ores, until the importation of cast iron from Sarawak and later from China. INVENTIONS AND DISCOVERIES - They learn to weave cotton, make glass ornaments, and cultivate lowland rice and dike fields of terraced fields utilizing spring water in mountain regions. - They also learned to build boats for trading purposes. - Spanish chronicles noted refined plank built warships called caracoa suited for interisland trade raids 10TH CENTURY A.D. - Filipinos from the Butuan were trading with Champa (Vietnam) and those from Ma-I (Mindoro) with China as noted in Chinese records containing several references to the Philippines. These archaeological findings indicated that regular trade relations between the Philippines, China and Vietnam had been well established from the 10th century to the 15th century A.D. TRADING - The People of Ma-I and San-Hsu (Palawan) traded bee wax, cotton, pearls, coconut heart mats, tortoise shell and medicinal betel nuts, panie cloth for porcelain, leads fishnets sinker, colored glass beads, iron pots, iron needles and tin. SOME PRESPANISH FILIPINO SCIENCE AND TECHNOLOGY - Curative values of plants extract use as medicine - Alphabet (Alibata) - Counting Methods - Weights - Measuring system (isang gatang) - Calendar based on the periods of moon - Banaue Rice Terraces SPANISH REGIME Religion the Catholic Church - The latter part of the 16th Century Development of schools: - Colegio de San Ildefonso-Cebu-1595 - Colegio de San Ignacio-Manila-1595 - Colegio De Nuestra Senora del Rosario-Manila 1597 - Colegio De San Jose-Manila-1601 Colegio De San Ildefonso De Cebu - In 1863 the colonial authorities issued a royal degree to reform the existing educational system. In 1871 the school of medicine and pharmacy were opened to UST, after 15 years it had granted the degree Of Licenciado En Medicina to 62 graduates. Medicine - Development of hospitals San Juan Lazaro hospital the oldest in the far east was founded in 1578. Roads and Bridges Among other Spanish contributions: - Arithmetic - Algebra - Geometry - Trigonometry - Physics - Hydrography - Meteorology - Navigation - Pilotage American Period and Post Commonwealth Era - BUREAU OF GOVERNMENT LABORATORIES (1901) - BUREAU OF SCIENCE (1905) - INSTITUTE OF SCIENCE (1946) RA 2067 OTHERWISE KNOWN AS THE “SCIENCE ACT OF 1958”. - This was enacted to integrate, coordinate, and intensify scientific and technological research and development and to foster invention including allocation of funds and other purposes. NATIONAL RESEARCH COUNCIL WAS ESTABLISHED ON DECEMBER 8, 1933. - Its Mandate (Nrcp) Promotes And Supports Fundamental Or Basic Research For The Continuing Total Improvement Of The Research Capability Of Individual Scientists Or Group Of Scientists; Provides Advice On Problems And Issues Of National Interest; Promotes Scientific And Technological Culture To All Sectors Of Society; And Fosters Linkages With Local And International Scientific Organizations For Enhanced Cooperation In The Development And Sharing Of Information NATIONAL RESEARCH COUNCIL WAS ESTABLISHED IN DECEMBER 8, 1933. - Its Mandate (NRCP) promotes and supports fundamental or basic research for the continuing total improvement of the research capability of individual scientists or group of scientists; provides advice on problems and issues of national interest; promotes scientific and technological culture to all sectors of society; and fosters linkages with local and international scientific organizations for enhanced cooperation in the development and sharing of information. It was during the American Period when Science was inclined towards: - Agriculture - Food Processing - Forestry - Medicine - Pharmacy - Nursing