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Received: 26 November 2019 Revised: 10 January 2020 Accepted: 19 January 2020 DOI: 10.1111/obr.13005 PEDIATRICS/PHYSIOLOGY Adipokines: A gear shift in puberty 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. 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Ann Epidemiol. 2017;27(3):187-93.e2. 16. Glass NA, Torner JC, Letuchy EM, et al. The relationship between greater prepubertal adiposity, subsequent age of maturation, and bone strength during adolescence. Journal of bone and mineral research: the official journal of the American Society for Bone and Min- eral Research. 2016;31(7):1455-1465. 17. Holmgren A, Niklasson A, Nierop AF, et al. Pubertal height gain is inversely related to peak BMI in childhood. Pediatr Res. 2017;81(3): 448-454. 18. Kaplowitz PB, Slora EJ, Wasserman RC, Pedlow SE, Herman- Giddens ME. Earlier onset of puberty in girls: relation to increased body mass index and race. Pediatrics. 2001;108(2):347-353. 19. Kelly Y, Zilanawala A, Sacker A, Hiatt R, Viner R. Early puberty in 11-year-old girls: Millennium Cohort Study findings. Arch Dis Child. 2017;102(3):232-237. 20. Lazzeri G, Tosti C, Pammolli A, et al. Overweight and lower age at menarche: evidence from the Italian HBSC cross-sectional survey. BMC Womens Health. 2018;18(1):168-174. thereby an early onset of obesity. leptin can inhibit the production of testosterone in boys and subse- quently inhibit the development of secondary sex characteristics affecting spermatogenesis. for other adipokines, like resistin and omentin, are present in the testes and ovaries suggesting a role in puberty or reproduction; 58, 71 however, their plausible function is still unknown. that adipokines may be key regulators in an early onset of puberty in both girls and boys with obesity, specifically by affecting the HPG axis during gonadarche. Future research should focus on assessing puberty onset by measuring consistent puberty markers and determine the percentage of body fat and its distribution and adipokines and hormone serum levels particularly involved in the HPG axis. CONFLICTS OF INTEREST The authors declare no conflict of interest. FUNDING INFORMATION This research was funded by Europees Fonds voor Regionale Ontwikkeling (EFRO), project BriteN 2016. ORCID Ilse A.C. Arnoldussen Amanda J. Kiliaan https://orcid.org/0000-0002-7395-5284 https://orcid.org/0000-0002-2158-6210 13, 14, 16-26, 29-32 Furthermore, several receptors Nevertheless, We conclude Search strategy We searched PubMed for articles published before Novem- ber 15th, 2019 using relevant keywords, including ‘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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Trends in menarcheal age between 1955 and 2009 in the Netherlands. PLoS ONE. 2013;8:e60056-e60056. 40. Kaplan HS, Lancaster JB. An evolutionary and ecological analysis of human fertility, mating patterns, and parental investment. Off- spring: Human fertility behavior in biodemographic perspective. 2003;1: 170-223. 41. Mitan LA. Menstrual dysfunction in anorexia nervosa. J Pediatr Adolesc Gynecol. 2004;17(2):81-85. 42. Xu H, Li P-H, Barrow TM, et al. Obesity as an effect modifier of the association between menstrual abnormalities and hypertension in young adult women: Results from Project ELEFANT. PLoS ONE. 2018; 13(11):e0207929-e0207929. 43. Tauqeer Z, Gomez G, Stanford FC. Obesity in women: insights for the clinician. J Womens Health (Larchmt). 2018;27(4):444-457. 44. de Ridder CM, Thijssen JH, Bruning PF, Van den Brande JL, Zonderland ML, Erich WB. Body fat mass, body fat distribution, and pubertal development: a longitudinal study of physical and hormonal sexual maturation of girls. J Clin Endocrinol Metab. 1992;75(2): 442-446. 45. Lassek W, Gaulin S. Brief communication: menarche is related to fat distribution. Am J Phys Anthropol. 2007;133(4):1147-1151. 46. Loomba-Albrecht LA, Styne DM. Effect of puberty on body composi- tion. Curr Opin Endocrinol Diabetes Obes. 2009;16:10-15. 47. Simonneaux V, Bahougne T. A multi-oscillatory circadian system times female reproduction. Front Endocrinol. 2015;6:1-15. 48. Marques P, Skorupskaite K, George JT, Anderson RA. Physiology of GNRH and gonadotropin secretion. In: Feingold KR, Anawalt B, Boyce A, et al., eds. Endotext. Endotext.org: South Dartmouth (MA); 2000. 49. Barcellos Gemelli IF, Farias EDS, Souza OF. Age at menarche and its association with excess weight and body fat percentage in girls in the Southwestern Region of the Brazilian Amazon. 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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 goverILLINOIS PROFESSIONAL TEACHING STANDARDS (2013) Standard 1 - Teaching Diverse Students – The competent teacher understands the diverse characteristics and abilities of each student and how individuals develop and learn within the context of their social, economic, cultural, linguistic, and academic experiences. The teacher uses these experiences to create instructional opportunities that maximize student learning. Knowledge Indicators – The competent teacher: 1A) understands the spectrum of student diversity (e.g., race and ethnicity, socioeconomic status, special education, gifted, English language learners (ELL), sexual orientation, gender, gender identity) and the assets that each student brings to learning across the curriculum; 1B) understands how each student constructs knowledge, acquires skills, and develops effective and efficient critical thinking and problem-solving capabilities; 1C) understands how teaching and student learning are influenced by development (physical, social and emotional, cognitive, linguistic), past experiences, talents, prior knowledge, economic circumstances and diversity within the community; 1D) understands the impact of cognitive, emotional, physical, and sensory disabilities on learning and communication pursuant to the Individuals with Disabilities Education Improvement Act (also referred to as “IDEA”) (20 USC 1400 et seq.), its implementing regulations (34 CFR 300; 2006), Article 14 of the School Code [105 ILCS 5/Art.14] and 23 Ill. Adm. Code 226 (Special Education); 1E) understands the impact of linguistic and cultural diversity on learning and communication; 1F) understands his or her personal perspectives and biases and their effects on one’s teaching; and 1G) understands how to identify individual needs and how to locate and access technology, services, and resources to address those needs. Performance Indicators – The competent teacher: 1H) analyzes and uses student information to design instruction that meets the diverse needs of students and leads to ongoing growth and achievement; 1I) stimulates prior knowledge and links new ideas to already familiar ideas and experiences; 1J) differentiates strategies, materials, pace, levels of complexity, and language to introduce concepts and principles so that they are meaningful to students at varying levels of development and to students with diverse learning needs; 1K) facilitates a learning community in which individual differences are respected; and 1L) uses information about students’ individual experiences, families, cultures, and communities to create meaningful learning opportunities and enrich instruction for all students. Standard 2 - Content Area and Pedagogical Knowledge – The competent teacher has in-depth understanding of content area knowledge that includes central concepts, methods of inquiry, structures of the disciplines, and content area literacy. The teacher creates meaningful learning experiences for each student based upon interactions among content area and pedagogical knowledge, and evidence-based practice. Knowledge Indicators – The competent teacher: 2A) understands theories and philosophies of learning and human development as they relate to the range of students in the classroom; 2B) understands major concepts, assumptions, debates, and principles; processes of inquiry; and theories that are central to the disciplines; 2C) understands the cognitive processes associated with various kinds of learning (e.g., critical and creative thinking, problem-structuring and problem-solving, invention, memorization, and recall) 2 and ensures attention to these learning processes so that students can master content standards; 2D) understands the relationship of knowledge within the disciplines to other content areas and to life applications; 2E) understands how diverse student characteristics and abilities affect processes of inquiry and influence patterns of learning; 2F) knows how to access the tools and knowledge related to latest findings (e.g., research, practice, methodologies) and technologies in the disciplines; 2G) understands the theory behind and the process for providing support to promote learning when concepts and skills are first being introduced; and 2H) understands the relationship among language acquisition (first and second), literacy development, and acquisition of academic content and skills. Performance Indicators – The competent teacher: 2I) evaluates teaching resources and materials for appropriateness as related to curricular content and each student’s needs; 2J) uses differing viewpoints, theories, and methods of inquiry in teaching subject matter concepts; 2K) engages students in the processes of critical thinking and inquiry and addresses standards of evidence of the disciplines; 2L) demonstrates fluency in technology systems, uses technology to support instruction and enhance student learning, and designs learning experiences to develop student skills in the application of technology appropriate to the disciplines; 2M) uses a variety of explanations and multiple representations of concepts that capture key ideas to help each student develop conceptual understanding and address common misunderstandings; 2N) facilitates learning experiences that make connections to other content areas and to life experiences; 2O) designs learning experiences and utilizes assistive technology and digital tools to provide access to general curricular content to individuals with disabilities; 2P) adjusts practice to meet the needs of each student in the content areas; and 2Q) applies and adapts an array of content area literacy strategies to make all subject matter accessible to each student. Standard 3 - Planning for Differentiated Instruction – The competent teacher plans and designs instruction based on content area knowledge, diverse student characteristics, student performance data, curriculum goals, and the community context. The teacher plans for ongoing student growth and achievement. Knowledge Indicators – The competent teacher: 3A) understands the Illinois Learning Standards (23 Ill. Adm. Code 1.Appendix D), curriculum development process, content, learning theory, assessment, and student development and knows how to incorporate this knowledge in planning differentiated instruction; 3B) understands how to develop short- and long-range plans, including transition plans, consistent with curriculum goals, student diversity, and learning theory; 3C) understands cultural, linguistic, cognitive, physical, and social and emotional differences, and considers the needs of each student when planning instruction; 3D) understands when and how to adjust plans based on outcome data, as well as student needs, goals, and responses; 3E) understands the appropriate role of technology, including assistive technology, to address student needs, as well as how to incorporate contemporary tools and resources to maximize student learning; 3 3F) understands how to co-plan with other classroom teachers, parents or guardians, paraprofessionals, school specialists, and community representatives to design learning experiences; and 3G) understands how research and data guide instructional planning, delivery, and adaptation. Performance Indicators – The competent teacher: 3H) establishes high expectations for each student’s learning and behavior; 3I) creates short-term and long-term plans to achieve the expectations for student learning; 3J) uses data to plan for differentiated instruction to allow for variations in individual learning needs; 3K) incorporates experiences into instructional practices that relate to a student’s current life experiences and to future life experiences; 3L) creates approaches to learning that are interdisciplinary and that integrate multiple content areas; 3M) develops plans based on student responses and provides for different pathways based on student needs; 3N) accesses and uses a wide range of information and instructional technologies to enhance a student’s ongoing growth and achievement; 3O) when planning instruction, addresses goals and objectives contained in plans developed under Section 504 of the Rehabilitation Act of 1973 (29 USC 794), individualized education programs (IEP) (see 23 Ill. Adm. Code 226 (Special Education)) or individual family service plans (IFSP) (see 23 Ill. Adm. Code 226 and 34 CFR 300.24; 2006); 3P) works with others to adapt and modify instruction to meet individual student needs; and 3Q) develops or selects relevant instructional content, materials, resources, and strategies (e.g., project-based learning) for differentiating instruction. Standard 4 - Learning Environment – The competent teacher structures a safe and healthy learning environment that facilitates cultural and linguistic responsiveness, emotional well-being, self-efficacy, positive social interaction, mutual respect, active engagement, academic risk-taking, self-motivation, and personal goal-setting. Knowledge Indicators – The competent teacher: 4A) understands principles of and strategies for effective classroom and behavior management; 4B) understands how individuals influence groups and how groups function in society; 4C) understands how to help students work cooperatively and productively in groups; 4D) understands factors (e.g., self-efficacy, positive social interaction) that influence motivation and engagement; 4E) knows how to assess the instructional environment to determine how best to meet a student’s individual needs; 4F) understands laws, rules, and ethical considerations regarding behavior intervention planning and behavior management (e.g., bullying, crisis intervention, physical restraint); 4G) knows strategies to implement behavior management and behavior intervention planning to ensure a safe and productive learning environment; and 4H) understands the use of student data (formative and summative) to design and implement behavior management strategies. Performance Indicators – The competent teacher: 4I) creates a safe and healthy environment that maximizes student learning; 4J) creates clear expectations and procedures for communication and behavior and a physical setting conducive to achieving classroom goals; 4K) uses strategies to create a smoothly functioning learning community in which students assume responsibility for themselves and one another, participate in decision-making, work collaboratively and independently, use appropriate technology, and engage in purposeful learning activities; 4 4L) analyzes the classroom environment and makes decisions to enhance cultural and linguistic responsiveness, mutual respect, positive social relationships, student motivation, and classroom engagement; 4M) organizes, allocates, and manages time, materials, technology, and physical space to provide active and equitable engagement of students in productive learning activities; 4N) engages students in and monitors individual and group-learning activities that help them develop the motivation to learn; 4O) uses a variety of effective behavioral management techniques appropriate to the needs of all students that include positive behavior interventions and supports; 4P) modifies the learning environment (including the schedule and physical arrangement) to facilitate appropriate behaviors and learning for students with diverse learning characteristics; and 4Q) analyzes student behavior data to develop and support positive behavior. Standard 5 - Instructional Delivery – The competent teacher differentiates instruction by using a variety of strategies that support critical and creative thinking, problem-solving, and continuous growth and learning. This teacher understands that the classroom is a dynamic environment requiring ongoing modification of instruction to enhance learning for each student. Knowledge Indicators – The competent teacher: 5A) understands the cognitive processes associated with various kinds of learning; 5B) understands principles and techniques, along with advantages and limitations, associated with a wide range of evidence-based instructional practices; 5C) knows how to implement effective differentiated instruction through the use of a wide variety of materials, technologies, and resources; 5D) understands disciplinary and interdisciplinary instructional approaches and how they relate to life and career experiences; 5E) knows techniques for modifying instructional methods, materials, and the environment to facilitate learning for students with diverse learning characteristics; 5F) knows strategies to maximize student attentiveness and engagement; 5G) knows how to evaluate and use student performance data to adjust instruction while teaching; and 5H) understands when and how to adapt or modify instruction based on outcome data, as well as student needs, goals, and responses. Performance Indicators – The competent teacher: 5I) uses multiple teaching strategies, including adjusted pacing and flexible grouping, to engage students in active learning opportunities that promote the development of critical and creative thinking, problem-solving, and performance capabilities; 5J) monitors and adjusts strategies in response to feedback from the student; 5K) varies his or her role in the instructional process as instructor, facilitator, coach, or audience in relation to the content and purposes of instruction and the needs of students; 5L) develops a variety of clear, accurate presentations and representations of concepts, using alternative explanations to assist students’ understanding and presenting diverse perspectives to encourage critical and creative thinking; 5M) uses strategies and techniques for facilitating meaningful inclusion of individuals with a range of abilities and experiences; 5N) uses technology to accomplish differentiated instructional objectives that enhance learning for each student; 5O) models and facilitates effective use of current and emerging digital tools to locate, analyze, evaluate, and use information resources to support research and learning; 5P) uses student data to adapt the curriculum and implement instructional strategies and materials according to the characteristics of each student; 5 5Q) uses effective co-planning and co-teaching techniques to deliver instruction to all students; 5R) maximizes instructional time (e.g., minimizes transitional time); and 5S) implements appropriate evidence-based instructional strategies. Standard 6 - Reading, Writing, and Oral Communication – The competent teacher has foundational knowledge of reading, writing, and oral communication within the content area and recognizes and addresses student reading, writing, and oral communication needs to facilitate the acquisition of content knowledge. Knowledge Indicators – The competent teacher: 6A) understands appropriate and varied instructional approaches used before, during, and after reading, including those that develop word knowledge, vocabulary, comprehension, fluency, and strategy use in the content areas; 6B) understands that the reading process involves the construction of meaning through the interactions of the reader's background knowledge and experiences, the information in the text, and the purpose of the reading situation; 6C) understands communication theory, language development, and the role of language in learning; 6D) understands writing processes and their importance to content learning; 6E) knows and models standard conventions of written and oral communications; 6F) recognizes the relationships among reading, writing, and oral communication and understands how to integrate these components to increase content learning; 6G) understands how to design, select, modify, and evaluate a wide range of materials for the content areas and the reading needs of the student; 6H) understands how to use a variety of formal and informal assessments to recognize and address the reading, writing, and oral communication needs of each student; and 6I) knows appropriate and varied instructional approaches, including those that develop word knowledge, vocabulary, comprehension, fluency, and strategy use in the content areas. Performance Indicators – The competent teacher: 6J) selects, modifies, and uses a wide range of printed, visual, or auditory materials, and online resources appropriate to the content areas and the reading needs and levels of each student (including ELLs, and struggling and advanced readers); 6K) uses assessment data, student work samples, and observations from continuous monitoring of student progress to plan and evaluate effective content area reading, writing, and oral communication instruction; 6L) facilitates the use of appropriate word identification and vocabulary strategies to develop each student’s understanding of content; 6M) teaches fluency strategies to facilitate comprehension of content; 6N) uses modeling, explanation, practice, and feedback to teach students to monitor and apply comprehension strategies independently, appropriate to the content learning; 6O) teaches students to analyze, evaluate, synthesize, and summarize information in single texts and across multiple texts, including electronic resources; 6P) teaches students to develop written text appropriate to the content areas that utilizes organization (e.g., compare/contrast, problem/solution), focus, elaboration, word choice, and standard conventions (e.g., punctuation, grammar); 6Q) integrates reading, writing, and oral communication to engage students in content learning; 6R) works with other teachers and support personnel to design, adjust, and modify instruction to meet students’ reading, writing, and oral communication needs; and 6S) stimulates discussion in the content areas for varied instructional and conversational purposes. Standard 7 - Assessment – The competent teacher understands and uses appropriate formative and summative assessments for determining student needs, monitoring student progress, measuring student 6 growth, and evaluating student outcomes. The teacher makes decisions driven by data about curricular and instructional effectiveness and adjusts practices to meet the needs of each student. Knowledge Indicators – The competent teacher: 7A) understands the purposes, characteristics, and limitations of different types of assessments, including standardized assessments, universal screening, curriculum-based assessment, and progress monitoring tools; 7B) understands that assessment is a means of evaluating how students learn and what they know and are able to do in order to meet the Illinois Learning Standards; 7C) understands measurement theory and assessment-related issues, such as validity, reliability, bias, and appropriate and accurate scoring; 7D) understands current terminology and procedures necessary for the appropriate analysis and interpretation of assessment data; 7E) understands how to select, construct, and use assessment strategies and instruments for diagnosis and evaluation of learning and instruction; 7F) knows research-based assessment strategies appropriate for each student; 7G) understands how to make data-driven decisions using assessment results to adjust practices to meet the needs of each student; 7H) knows legal provisions, rules, and guidelines regarding assessment and assessment accommodations for all student populations; and 7I) knows assessment and progress monitoring techniques to assess the effectiveness of instruction for each student. Performance Indicators – The competent teacher: 7J) uses assessment results to determine student performance levels, identify learning targets, select appropriate research-based instructional strategies, and implement instruction to enhance learning outcomes; 7K) appropriately uses a variety of formal and informal assessments to evaluate the understanding, progress, and performance of an individual student and the class as a whole; 7L) involves students in self-assessment activities to help them become aware of their strengths and needs and encourages them to establish goals for learning; 7M) maintains useful and accurate records of student work and performance; 7N) accurately interprets and clearly communicates aggregate student performance data to students, parents or guardians, colleagues, and the community in a manner that complies with the requirements of the Illinois School Student Records Act [105 ILCS 10], 23 Ill. Adm. Code 375 (Student Records), the Family Educational Rights and Privacy Act (FERPA) (20 USC 1232g) and its implementing regulations (34 CFR 99; December 9, 2008); 7O) effectively uses appropriate technologies to conduct assessments, monitor performance, and assess student progress; 7P) collaborates with families and other professionals involved in the assessment of each student; 7Q) uses various types of assessment procedures appropriately, including making accommodations for individual students in specific contexts; and 7R) uses assessment strategies and devices that are nondiscriminatory, and take into consideration the impact of disabilities, methods of communication, cultural background, and primary language on measuring knowledge and performance of students. Standard 8 - Collaborative Relationships – The competent teacher builds and maintains collaborative relationships to foster cognitive, linguistic, physical, and social and emotional development. This teacher works as a team member with professional colleagues, students, parents or guardians, and community members. Knowledge Indicators – The competent teacher: 8A) understands schools as organizations within the larger community context; 7 8B) understands the collaborative process and the skills necessary to initiate and carry out that process; 8C) collaborates with others in the use of data to design and implement effective school interventions that benefit all students; 8D) understands the benefits, barriers, and techniques involved in parent and family collaborations; 8E) understands school- and work-based learning environments and the need for collaboration with all organizations (e.g., businesses, community agencies, nonprofit organizations) to enhance student learning; 8F) understands the importance of participating on collaborative and problem-solving teams to create effective academic and behavioral interventions for all students; 8G) understands the various models of co-teaching and the procedures for implementing them across the curriculum; 8H) understands concerns of families of students with disabilities and knows appropriate strategies to collaborate with students and their families in addressing these concerns; and 8I) understands the roles and the importance of including students with disabilities, as appropriate, and all team members in planning individualized education programs (i.e, IEP, IFSP, Section 504 plan) for students with disabilities. Performance Indicators – The competent teacher: 8J) works with all school personnel (e.g., support staff, teachers, paraprofessionals) to develop learning climates for the school that encourage unity, support a sense of shared purpose, show trust in one another, and value individuals; 8K) participates in collaborative decision-making and problem-solving with colleagues and other professionals to achieve success for all students; 8L) initiates collaboration with others to create opportunities that enhance student learning; 8M) uses digital tools and resources to promote collaborative interactions; 8N) uses effective co-planning and co-teaching techniques to deliver instruction to each student; 8O) collaborates with school personnel in the implementation of appropriate assessment and instruction for designated students; 8P) develops professional relationships with parents and guardians that result in fair and equitable treatment of each student to support growth and learning; 8Q) establishes respectful and productive relationships with parents or guardians and seeks to develop cooperative partnerships to promote student learning and well-being; 8R) uses conflict resolution skills to enhance the effectiveness of collaboration and teamwork; 8S) participates in the design and implementation of individualized instruction for students with special needs (i.e., IEPs, IFSP, transition plans, Section 504 plans), ELLs, and students who are gifted; and 8T) identifies and utilizes community resources to enhance student learning and to provide opportunities for students to explore career opportunities. Standard 9 - Professionalism, Leadership, and Advocacy – The competent teacher is an ethical and reflective practitioner who exhibits professionalism; provides leadership in the learning community; and advocates for students, parents or guardians, and the profession. Knowledge Indicators – The competent teacher: 9A) evaluates best practices and research-based materials against benchmarks within the disciplines; 9B) knows laws and rules (e.g., mandatory reporting, sexual misconduct, corporal punishment) as a foundation for the fair and just treatment of all students and their families in the classroom and school; 9C) understands emergency response procedures as required under the School Safety Drill Act [105 ILCS 128/1], including school safety and crisis intervention protocol, initial response 8 actions (e.g., whether to stay in or evacuate a building), and first response to medical emergencies (e.g., first aid and life-saving techniques); 9D) identifies paths for continuous professional growth and improvement, including the design of a professional growth plan; 9E) is cognizant of his or her emerging and developed leadership skills and the applicability of those skills within a variety of learning communities; 9F) understands the roles of an advocate, the process of advocacy, and its place in combating or promoting certain school district practices affecting students; 9G) understands local and global societal issues and responsibilities in an evolving digital culture; and 9H) understands the importance of modeling appropriate dispositions in the classroom. Performance Indicators – The competent teacher: 9I) models professional behavior that reflects honesty, integrity, personal responsibility, confidentiality, altruism and respect; 9J) maintains accurate records, manages data effectively, and protects the confidentiality of information pertaining to each student and family; 9K) reflects on professional practice and resulting outcomes; engages in self-assessment; and adjusts practices to improve student performance, school goals, and professional growth; 9L) communicates with families, responds to concerns, and contributes to enhanced family participation in student education; 9M) communicates relevant information and ideas effectively to students, parents or guardians, and peers, using a variety of technology and digital-age media and formats; 9N) collaborates with other teachers, students, parents or guardians, specialists, administrators, and community partners to enhance students’ learning and school improvement; 9O) participates in professional development, professional organizations, and learning communities, and engages in peer coaching and mentoring activities to enhance personal growth and development; 9P) uses leadership skills that contribute to individual and collegial growth and development, school improvement, and the advancement of knowledge in the teaching profession; 9Q) proactively serves all students and their families with equity and honor and advocates on their behalf, ensuring the learning and well-being of each child in the classroom; 9R) is aware of and complies with the mandatory reporter provisions of Section 4 of the Abused and Neglected Child Reporting Act [325 ILCS 5/4]; 9S) models digital etiquette and responsible social actions in the use of digital technology; and 9T) models and teaches safe, legal, and ethical use of digital information and technology, including respect for copyright, intellectual property, and the appropriate documentation of sources.Hsk Standard Course 2 μάθημα 7Make a multiple choice test with the follwo1. Causation 13. Abetting 25. Restitution 2. Direct Evidence 14. Private Law 26. Writ of Summons 3. Automatism 15. Prejudice 27. Actus Reus 4. Self-Defense 16. Contributory Negligence 28. Net Family Property 5. Reasonable Limits Clause 17. Duress 29. Poisoned Environment 6. Standard of Care 18. Circumstantial Evidence 30. Mediation 7. Habeus Corpus 19.. Public Law 31. Act 8. Oakes Test 20. Accessory After the Fact 32. Prima Facie 9. Pecuniary 21. Hybrid Offence 33. Opinion Evidence 10. Mens Rea 22. Aiding 34. Indictable Offence 11. Marriage Breakdown 23. Manslaughter 35.Unintentional Discrimination 12. Crown 24. Empanellinging terms:Good day this is Chris today we will be doing a quick walkthrough on ISO 14001 2015 Environmental Management System and its main clauses let's get started ISO 14001 2015 Environmental Management System is a globally recognized standard for environment Management systems or EMS an EMS is a framework that organizations use to manage their environmental impact comply with regulations and improve their environmental performance the standard outlines are requirements for an EMS including the development of an environmental policy the identification of environmental aspects and impacts the establishment of objectives and targets the implementation of operational control monitoring and measurement systems and the ongoing review and Improvement of the system ISO 14001 is a flexible standard that can be used by organizations of any size or type regardless of their environment impact or level of environment performance it provides a practical framework for organizations to manage their environmental impact reduce environment risks and demonstrate their commitment on sustainability to their stakeholders here is the standard that provides a structured approach to develop an EMS which includes several key steps one organizations must develop an environmental policy that outlines their commitment to environmental sustainability this policy should be communicated to all employees and stakeholders two organizations must identify their environmental aspects and impacts this involves identifying the activities products and services that have an impact on the environment as well as the potential environmental consequences of those impacts three once the environmental aspects and the impacts have been identified organizations must establish environmental objectives and targets these objectives and targets should be specific measurable achievable relevant and time-bound 4. after setting objectives and targets organizations must Implement operational controls and establish monitoring and measurement systems to ensure that they are meeting their objectives and targets finally organizations must review and continually improve their EMS this involves conducting regular audits reviewing the EMS to ensure that it remains relevant and effective and making any necessary changes or improvements the main Clause of iso 14001 2015 apart from its scope normative references and terms and conditions that the main Clauses of iso 14001 2015 can be listed as context of the organization leadership planning support operation performance evaluation and Improvement Clause 4.0 context of the organization is about understanding the organization and its context understanding the needs and expectations of the interested parties determining the scope of the Environmental Management System EMS and Environmental Management System itself Clause 5.0 talks about leadership and commitment Environmental Policy organizational roles responsibility and authorities Clause 6.0 planning focuses on actions to address risk and opportunities as well as environmental objectives and planning to achieve them Clause 7.0 support are detailed requirements on resources competence awareness communication that includes external and internal communication documented information that involves creating updating in control of documented information Clause 8.0 operation talks about operational planning and control as well as emergency preparedness and response overall the design of iso 14001 2015 provides guidelines to form a system that is structured to cater the requirements of stakeholder needs and expectations to drive life cycle perspective and Energy Efficiency as pictured here Clause 9.0 performance evaluation provides guidelines to monitoring measurement analysis and evaluation evaluation compliance and management review an additional note here is that ISO 19011 2018 guidelines for auditing Management Systems which is an audit process that will determine the scope to establish the audit criteria by collecting evidence evaluating the evidence and then draw a conclusion based on the findings as pictured here [Music] finally Clause 10.0 Improvement talks about how Improvement is an integral factor to an effective Environmental Management system through General non-conformity and corrective action and continual Improvement talking about Improvement it is always continual in putting efforts towards the betterment of the existing system here is a snapshot of the main Clauses of iso 14001 2015 [Music] I hope you find this video useful we are industry experts specialized in management system consultancy and Industry relevant corporate training give us a call and let us help you drive your business excellence and upskill your employees to elevate workplace efficiency [Music] CREATE 10 MCQ AND 2 SAQ QUESTIONS BASED ON THE ABOVE PARAGRAPHTPE 3: Understanding and Organizing Subject Matter for Student Learning Elements: Mild to Moderate Support Candidates will: U3.1 Demonstrate knowledge of subject matter, including the adopted California State Standards and curriculum frameworks. U3.2 Use knowledge about students and learning goals to organize the curriculum to facilitate student understanding of subject matter and make accommodations and/or modifications as needed to promote student access to the curriculum. U3.3 Plan, design, implement, and monitor instruction consistent with current subjectspecific pedagogy in the content area(s) of instruction, and design and implement disciplinary and cross-disciplinary learning sequences, including integrating the visual and performing arts as applicable to the discipline.1 U3.4 Individually and through consultation and collaboration with other educators and members of the larger school community, plan for effective subject matter instruction and use multiple means of representing, expressing, and engaging students to demonstrate their knowledge. U3.5 Adapt subject matter curriculum, organization, and planning to support the acquisition and use of academic language within learning activities to promote the subject matter knowledge of all students, including the full range of English learners, Standard English learners, students with disabilities, and students with other learning needs in the least restrictive environment. U3.6 Use and adapt resources, standards-aligned instructional materials, and a range of technology, including assistive technology, to facilitate students' equitable access to the curriculum. U3.7 Model and develop digital literacy by using technology to engage students and support their learning, and promote digital citizenship, including respecting copyright law, understanding fair use guidelines and the use of Creative Commons license, and maintaining Internet security. U.3.8 Demonstrate knowledge of effective teaching strategies aligned with the internationally recognized educational technology standards. MM3.1 Effectively adapt, modify, accommodate, and/or differentiate the instruction of students with identified disabilities in order to facilitate access to the Least Restrictive Environment (LRE). MM3.2 Demonstrate knowledge of disabilities and their effects on learning, skills development, social-emotional development, mental health, and behavior, and how to access and use related services and additional supports to organize and support effective instruction. MM3.3 Demonstrate knowledge of atypical development associated with various disabilities and risk conditions (e.g. orthopedic impairment, autism spectrum disorders, cerebral palsy), as well as resilience and protective factors (e.g. attachment, temperament), and their implications for learning. Question 1 Category: Current Events Question: What was the primary demand of the Kenyan Gen Z protesters featured in the BBC documentary Unmasked: The Truth Behind the Gen Z Protests? Options: A) Free education B) Repeal of the Finance Bill 2024 C) Climate change action D) New elections Correct Answer: B) Repeal of the Finance Bill 2024 Explanation: The BBC documentary highlights that Kenyan youth protested to demand the repeal of the Finance Bill 2024, which proposed tax hikes raising $2.7 billion. Question 2 Category: Science Question: Which gas, discovered on the sun before Earth, is the second most abundant element in the universe? Options: A) Hydrogen B) Oxygen C) Helium D) Nitrogen Correct Answer: C) Helium Explanation: Helium was first detected in the sun’s spectrum in 1868 and is the second most abundant element after hydrogen in the universe. Question 3 Category: Current Events Question: Which Kenyan city was the epicenter of the Gen Z protests covered in the BBC documentary Unmasked: The Truth Behind the Gen Z Protests? Options: A) Mombasa B) Nairobi C) Kisumu D) Eldoret Correct Answer: B) Nairobi Explanation: Nairobi, Kenya’s capital, was the main hub for the #OccupyParliament protests, with significant events like the Parliament breach occurring there, as shown in the documentary. Question 4 Category: History Question: Which empire, known for its vast trade networks, was centered in modern-day Turkey and lasted until the early 20th century? Options: A) Roman Empire B) Ottoman Empire C) Mongol Empire D) Byzantine Empire Correct Answer: B) Ottoman Empire Explanation: The Ottoman Empire, spanning over 600 years until 1922, was a major trade and cultural power centered in modern-day Turkey. Question 5 Category: Current Events Question: According to the BBC documentary, what technology helped document evidence of police brutality during the Kenyan Gen Z protests? Options: A) Drones B) Smartphone videos C) Facial recognition software D) Satellite tracking Correct Answer: B) Smartphone videos Explanation: The documentary used smartphone videos from protesters and bystanders, analyzed via open-source data, to document police brutality during the 2024 protests. Question 6 Category: Geography Question: What is the smallest country in the world by land area? Options: A) Monaco B) Vatican City C) San Marino D) Liechtenstein Correct Answer: B) Vatican City Explanation: Vatican City, with an area of about 44 hectares, is the smallest sovereign state in the world by land area. Question 7 Category: Current Events Question: What hashtag became synonymous with the Kenyan Gen Z protests, as featured in the BBC documentary Unmasked: The Truth Behind the Gen Z Protests? Options: A) #KenyaRising B) #OccupyParliament C) #TaxRevolt D) #GenZFight Correct Answer: B) #OccupyParliament Explanation: The #OccupyParliament hashtag was widely used by protesters to rally against the Finance Bill 2024, as documented by the BBC. Question 8 Category: Entertainment Question: Which actor starred as the lead in the 2023 film Barbie and also played a role in La La Land? Options: A) Emma Stone B) Margot Robbie C) Zendaya D) Saoirse Ronan Correct Answer: B) Margot Robbie Explanation: Margot Robbie starred as Barbie in the 2023 film and played a supporting role in La La Land (2016). Question 9 Category: Sports Question: Which sport is played at the Wimbledon Championships? Options: A) Cricket B) Rugby C) Tennis D) Golf Correct Answer: C) Tennis Explanation: Wimbledon, held annually in London, is the oldest and one of the most prestigious tennis tournaments in the world. Question 10 Category: Technology Question: In web development, what does the acronym “CSS” stand for? Options: A) Computer Style System B) Cascading Style Sheets C) Creative Script Syntax D) Centralized Style Standard Correct Answer: B) Cascading Style Sheets Explanation: CSS (Cascading Style Sheets) is used to style and format the appearance of web pages written in HTML.Nutrition refers to the science that deals with the various factors of which food is composed and the way in which proper nourishment is brought about. Home Economics and Livelihood Education 7 Seibo College 152 Human nutrition involves properly feeding the people. It is therefore important to learn more about nutrition, taking into consideration the three (3) important factors: a. the food we eat b. the way it is digested, absorbed and used in the tissues of the body c. the kind of people for whom the food is intended Good health or “wellness” is not a matter of chance. Good health is a product of good nutrition which is the result of an adequate supply of essential nutrients in your body. Lack of these nutrients lead to illness or a condition known as “malnutrition”. Malnutrition occurs if there is an imbalance intake of nutrients or an inadequacy of one or any of the nutrients. Malnutrition are manifested in the following cases: 1. obesity due to overeating- Obesity occurs when a person eats more than what the body requires under normal condition. This results in an excess supply of calories that leads to obesity or overnutrition. 2. stunted growth of children due to lack of protein- If there is no sufficient supply of carbohydrates or fats protein is used by the body as an alternative source of energy. 3. under weight due to lack of carbohydrates- If the total amount of nutrients provided by the diet is insufficient , it results to undernutrition. What is good nutrition? Home Economics and Livelihood Education 7 Seibo College 153 What are the causes of malnutrition? 1. ignorance or lack of knowledge about proper food intake 2. low standard of living 3. limited food supply 4. emergence of calamities or social unrest 5. increased family size 6. poor eating habits What are food habits? Food habits mean one’s attitude towards food. If the body is fed by junk foods and became over/under supplied with particular vitamins, protein or other nutrients then the body will suffer from malnutrition. Let us identify the factors affecting food habits. Education – knowledge about nutrition will help one to make wise decision about food. Foods available - The kinds of food available to you usually are the foods you eat. Some foods can grow only in certain types of geographic locations and this determines the foods available in such locations Religion - What foods people can eat or cannot eat have been dictated by their religious beliefs. For example, Moslems do not eat pork because Islam forbids them to eat it. Home Economics and Livelihood Education 7 Seibo College 154 Ethnicity – members of cultural groups formed their own living patterns which include food customs. It includes what food can or cannot be eaten. Income/economic status – the type of food you choose depends on how money you have. Income dictates what food you can eat and how you eat them. Convenience -. Meal management practices affect food habits because you can only prepare and eat foods you can easily cook with the facilities and the knowledge you have. Food habit refers to the way in which different people select , cook, serve and eat food that are available to them. Home Economics and Livelihood Education 7 Seibo College 155 Look at the diagram below for a better understanding. FACTORS THAT AFFECT FOOD HABITS FOOD HABITS Education Foods available Religion Convenience Economic status Ethnicit