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The Devil in the White City Plans for a Hotel
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Can you make me a 40 question quiz from the following information? he story of coffee has all the elements of a bestselling novel, such as chance happenings, luck, political intrigue, the high seas and great wealth. With research, you will find many stories and dates when this happened and dates when that happened. Often these stories and dates will conflict with each other. Whatever the history, coffee has become one of the most important trading commodities in the world. Being second only to oil and being one of the most popular beverages, behind tea, beer and of course, water. Coffee growing is a very labour-intensive operation and it provides important trading income for many nations and people throughout the world. The most famous story about the origin of coffee is the story of Kaldi a goat herder from Ethiopia. It is said he noticed that his goats became very active after eating the red berries of a certain plant. He tried a few himself and noticed the stimulating effect of the berries. It is then said that monks started drinking a beverage made from the berries to help stay awake for the prayers; this would have been around 1000 AD. Over the next few hundred years the Arab world started to use the berries as a beverage and coffee was born. In those early years, coffee was mostly confined to the Muslim world with the export of coffee plants and seeds banned. But coffee could not be hidden forever so eventually coffee was introduced to Constantinople and coffee houses were opened in 1475. European traders then brought coffee back to Europe by approximately 1600. At first, coffee was met with a hostile reaction, with some Christians calling it the âDevilâs Drinkâ and asking Pope Vincent III to ban the beverage. He tried coffee and liked it so much that he is claimed to have said âThis beverage is so delicious that it would be a sin to let only misbelievers drink it! Letâs defeat Satan by blessing this beverage, which contains nothing objectionable to a Christian!â Coffee shops sprung up in every city and became an important social and networking place to meet. This tradition continues today with the French word for coffee being âCafĂ©â. Coffee is said to have changed the social fabric of society by providing a popular non-alcoholic alternative to beer and wine. For the first time in recorded history people were not drunk all the time. Coffee today is grown and enjoyed worldwide and is one of the few crops that small farmers in third-world countries can profitably export. The coffee plant is a tree that is pruned to grow to a height of approximately three metres. This makes cultivating the beans easier as most of the beans are handpicked. The plant has white flowers similar to jasmine that grow in clusters and set to become red cherry-like fruit; beneath the red skin are two pips which are the coffee beans. Because the berries ripen at varying times the fruit must be handpicked to select only those beans ripe for harvest. This requires the picker to pick from the same plant many times and is very labour intensive. This is why coffee is grown in developing countries where labour is cheaper and foreign income is needed. Coffee plants grow best in a mountain tropical climate between the Tropic of Capricorn and the Tropic of Cancer. This mountainous land is another reason why machine picking is very difficult and hand picking is preferred. There are two main species of coffee grown today: Coffee Arabica. Coffee Robusta. Robusta grows at lower altitudes and produces a larger crop than Arabica; therefore, it is cheaper to produce Arabica is the most popular and generally considered to give superior flavour. Most Robusta is grown in Asia and Africa. About 75% of coffee grown is Arabica and 25% Robusta. Robusta is more often used as a blend with Arabica rather than a standalone coffee; used as a filler coffee in the production of instant or to add extra caffeine to an Arabica coffee for the European markets. Robusta is higher in caffeine than Arabica, but the flavour is not as palatable as the more popular Arabica bean. Coffee is produced in about 60 countries throughout the world but production is dominated by three countries producing approximately half the crop: Brazil, Vietnam and Colombia.The Devil in the White City Reading 1Review of Devil in the White City 2The cytoskeleton is a network of thin tubes and filaments that crisscrosses the cytosol. The tubes and filaments give shape to the cell from the inside in the same way that tent poles support the shape of a tent. The cytoskeleton also acts as a system of internal tracks, shown in Figure 4-18, on which items move around inside the cell. The cytoskeletonâs functions are based on several struc- tural elements. Three of these are microtubules, microfilaments, and intermediate filaments, shown and described in Table 4-2. Microtubules Microtubules are hollow tubes made of a protein called tubulin. Each tubulin molecule consists of two slightly different subunits. Microtubules radiate outward from a central point called the centrosome near the nucleus. Microtubules hold organelles in place, maintain a cellâs shape, and act as tracks that guide organelles and molecules as they move within the cell. Microfilaments Finer than microtubules, microfilaments are long threads of the beadlike protein actin and are linked end to end and wrapped around each other like two strands of a rope. Microfilaments con- tribute to cell movement, including the crawling of white blood cells and the contraction of muscle cells. Intermediate Filaments Intermediate filaments are rods that anchor the nucleus and some other organelles to their places in the cell. They maintain the inter- nal shape of the nucleus. Hair-follicle cells produce large quantities of intermediate filament proteins. These proteins make up most of the hair shaft. 84 CHAPTER 4 TABLE 4-2 The Structure of the Cytoskeleton Property Microtubules Microfilaments Intermediate filaments Structure hollow tubes made of two strands of intertwined protein fibers coiled into coiled protein protein cables Protein subunits tubulin, with two subunits: Ă„ actin one of several types of and â« tubulin fibrous proteins Main function maintenance of cell shape; cell maintenance and changing of maintenance of cell shape; motility (in cilia and flagella); cell shape; muscle contraction; anchor nucleus and other chromosome movement; movement of cytoplasm; cell organelles; maintenance of organelle movement motility; cell division shape of nucleus Shape Microtubules provide a path for organelles and molecules as they move throughout the cell. FIGURE 4-18 Microtubules Nucleus Endoplasmic reticulum Mitochondrion Ribosomes Copyright © by Holt, Rinehart and Winston. All rights reserved. Copyright © by Holt, Rinehart and Winston. All rights reserved. CELL STRUCTURE AND FUNCTION 85 1. Explain how the fluid mosaic model describes the plasma membrane. 2. List three cellular functions that occur in the nucleus. 3. Describe the organelles that are found in a eukaryotic cell. 4. Identify two characteristics that make mitochon- dria different from other organelles. 5. Contrast three types of cytoskeletal fibers. CRITICAL THINKING 6. Relating Concepts If a cell has a high energy requirement, would you expect the cell to have many mitochondria or few mitochondria? Why? 7. Analyzing Information How do scientists think that mitochondria originated? Why? 8. Analyzing Statements It is not completely accurate to say that organelles are floating freely in the cytosol. Why not? SECTION 3 REVIEW During cell division, centrioles organize microtubules that pull the chromosomes (orange) apart. The centrioles are at the center of rays of microtubules, which have been stained green with a fluorescent dye. FIGURE 4-20 Cilia and Flagella Cilia (SIL-ee-uh) and flagella (fluh-JEL-uh) are hairlike structures that extend from the surface of the cell, where they assist in movement. Cilia are short and are present in large numbers on certain cells, whereas flagella are longer and are far less numerous on the cells where they occur. Cilia and flagella have a membrane on their outer surface and an internal structure of nine pairs of micro- tubules around two central tubules, as Figure 4-19 shows. Cilia on cells in the inner ear vibrate and help detect sound. Cilia cover the surfaces of many protists and ârowâ the protists through water like thousands of oars. On other protists, cilia sweep water and food particles into a mouthlike opening. Many kinds of protists use flagella to propel themselves, as do human sperm cells. Centrioles Centrioles consist of two short cylinders of microtubules at right angles to each other and are situated in the cytoplasm near the nuclear envelope. Centrioles occur in animal cells, where they organize the microtubules of the cytoskeleton during cell division, as shown in Figure 4-20. Plant cells lack centrioles. Basal bodies have the same structure that centrioles do. Basal bodies are found at the base of cilia and flagella and appear to organize the devel- opment of cilia and flagella. 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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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. 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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 goverWhereâs the Joey? What's a Joey? A joey is a baby marsupial (mar-SOO-pee-ul). A marsupial is an unusual type of animal. Its babies are carried in a pouch, or pocket, on the mother's belly. As it grows, the little joey stays hidden inside the pouch. Safe inside, the tiny joey drinks milk and grows while it is carried around. Even after it can walk, the joey may still ride in mom's pouch. There are over three hundred types of marsupials. Most of them live in Australia (aw-STRAYL-yuh) and eat plants. Let's look at a few kinds of marsupials and their joeys. A Jumping Joey This joey stays in its mother's pouch for eight months while it grows very tall. Its feet and tail grow very long. too. Can you guess what it is? It's a red kangaroo! A red kangaroo is the largest marsupial. It can stand over six feet tall and weigh 200 lbs (91 kg). It can jump 30 feet (9 m) with each leap! A Joey That Lives in a Tree When grown, this little joey will look like a furry teddy bear with big ears. It will live most of its life sitting in trees and eating leaves. Can you guess what it is? It's a koala! A koala lives, eats, and sleeps in eucalyptus (yoo-kuh-LIP-tus) trees. It is happy just to sit anp eat lots of leaves every day. A koala usually only walks around at night. Joey the Screamer This marsupial mom might carry three or four noisy joeys in her pouch at one time. Her little joeys can scream very loudly. What are they? They are Tasmanian devils! The Tasmanian devil gets its name from its loud screams, sharp teeth, bad smell, and wild look. It is a meat-eater, and lives only on the island of Tasmania (taz-MAY-nee-uh). Protecting the Marsupials Most marsupials eat plants, and many, like the koala, live quietly in forests. When those forests are cut down, their homes, food, and safety are lost. Other marsupials have lost their sources of food to herds of grazing cows or growing cities. Marsupials Are Special Animals Most marsupials and their joeys live in only one place on Earth. We need to protect their special habitats and food sources-so we will always know where the joeys are.What is the page mainly about? (Answer: C â Homes meet a basic need) A) House colors B) Old buildings C) Homes meet a basic need â D) Travel What basic need do homes give? (Answer: B â Shelter) A) Food B) Shelter â C) Clothes D) Money What does âbasic needâ mean here? (Answer: C â Something people must have to live) A) Something nice to have B) A school rule C) Something people must have to live â D) A weekend plan Homes keep people ______ and ______. What are the two words from the page? (Answer: B â dry / safe) A) rich / tall B) dry / safe â C) loud / fast D) clean / funny What else are homes for, according to the text? (Answer: B â Eating, sleeping, and being with family and friends) A) Shopping B) Eating, sleeping, and being with family and friends â C) Driving D) Fighting What does the heading âMeeting our needsâ tell you? (Answer: B â explains how homes fit the local climate) A) A joke is coming B) This part explains how homes fit the local climate â C) It is a story D) It lists prices What does âclimateâ mean on this page? (Answer: C â the usual weather of a place) A) Yesterdayâs forecast B) A big storm C) The usual weather of a place â D) Room temperature Which roof is best for cold, snowy places? (Answer: D â Slanted) A) Flat B) Dome C) Glass D) Slanted â Why is a slanted roof helpful in snowy places? (Answer: B â snow slides off more easily) A) It is cheaper B) Snow slides off more easily â C) Birds like it D) It is quieter Why do many houses in hot places have many windows? (Answer: B â to let air move through and keep people cool) A) To block all light B) To let air move through and keep people cool â C) To make walls heavy D) To reduce street noise Which detail best supports âclimate changes home designâ? (Answer: C â Hot â many windows; Snowy â slanted roofs) A) People like blue walls B) Kitchens are big C) Hot â many windows; Snowy â slanted roofs â D) Cities are crowded What does the caption about a traditional Japanese house show? (Answer: C â People sit on mats on the floor to eat) A) People eat outdoors B) Families donât eat together C) People sit on mats on the floor to eat â D) People stand to eat Which sentence is LEAST connected to the main idea of the page? (Answer: D â Blue walls are relaxing) A) Homes protect people from weather B) Roofs can change with climate C) Windows help rooms stay cool D) Blue walls are relaxing â Which text structure organizes the right paragraph? (Answer: C â Causeâeffect) A) Timeline B) Problemâsolution C) Causeâeffect â D) Description only What is the authorâs purpose? (Answer: B â to explain how homes meet a human need) A) To sell houses B) To explain how homes meet a human need â C) To tell a funny story D) To give building laws What can you guess about a flat roof in a snowy place? (Answer: B â snow can pile up and be unsafe) A) Best choice B) Snow can pile up and be unsafe â C) Always cheaper D) Warmer in summer Which page feature helps you find ideas quickly? (Answer: C â Headings and photo captions) A) Rhyme B) Dialogue C) Headings and photo captions â D) Footnotes Which sentence is the best summary of the page? (Answer: C â Homes give shelter; designs change with climate) A) Houses are beautiful in winter B) People prefer bright colors C) Homes give shelter; designs change with climate (slanted roofs, many windows) â D) Windows are the most important part True/False or Short Answer (5) True/False: All homes have the same purpose, even if they look different. (Answer: True) True/False: In hot places, houses usually have fewer windows to keep heat in. (Answer: False â hot places â many windows for airflow/cooling) Short Answer (1â3 words): Homes provide shelter to keep people _____ and _____. (Answer: dry; safe) Short Answer (one example): Write one climate â design pair from the page. (Answer: cold/snowy â slanted roof OR hot â many windows) True/False: The photo shows people in Japan eating on mats on the floor. (Answer: True)Angels are spiritual beings. They do not have physical bodies. They are His servants; they obey God and do His will. Angels appear to people only when God has a purpose for them to be seen. People have entertained angels without being aware of it because the angels took on the appearance of ordinary men. They have appeared to people as bright and shining beings. In the Bible, angels have told people not to be afraid. Fallen angels, or demons, rebelled against God and followed Satan. As a result, they were cast out of heaven. The devil, or Satan, is one of these fallen angels. He is God's enemy. Satan was created as a beautiful angel, but his pride led to his downfall. God is infinitely more powerful than Satan, and God has set limits on Satan's temporary power on the earth. Satan tempts Christians to sin and causes some trouble in their life. However, Christians have various ways of overcoming temptation and staying true to the Lord despite the trouble. Being tempted to sin is not a sin; even Jesus was tempted but He never sinned. Christians are tempted by the devil, by their sinful nature, and by other people. Some of the ways that Christians can overcome temptation are by fleeing tempting situations, memorizing and applying Bible verses, exercising self-control, and keeping strong in their faith and their relationship with God.