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STARS 2 LETTERS "Q"-"R"
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STARS 2 LETTERS Q-RSTARS 2 LETTERS P+Q+RStars 2 Letters P +Q +RGenerate all of these 25 questions Part A: Each correct answer is worth 5. 1. The regular pentagon shown has a side length of 2 cm. The perimeter of the pentagon is (A) 2 cm (B) 4 cm (C) 6 cm (D) 8 cm (E) 10 cm 2 cm 2. The faces of a cube are labelled with 1, 2, 3, 4, 5, and 6 dots. Three of the faces are shown. What is the total number of dots on the other three faces? (A) 6 (B) 8 (C) 10 (D) 12 (E) 15 3. The equation that best represents \a number increased by _ve equals 15" is (A) n 5 = 15 (B) n _ 5 = 15 (C) n + 5 = 15 (D) n + 15 = 5 (E) n _ 5 = 15 4. The line graph shows the number of bobbleheads sold at a store each year. The sale of bobbleheads increased the most between (A) 2016 and 2017 (B) 2017 and 2018 (C) 2018 and 2019 (D) 2019 and 2020 (E) 2020 and 2021 Number of 2016 2017 2018 2019 2020 Year Sale of Bobbleheads 2021 Bobbleheads 20 40 60 80 5. Starting at 72, Aryana counts down by 11s: 72; 61; 50; : : : . What is the last number greater than 0 that Aryana will count? (A) 4 (B) 5 (C) 6 (D) 7 (E) 8 6. In the diagram, \ABC = 90_. The value of x is (A) 68 (B) 23 (C) 56 (D) 28 (E) 26 Day of the Week 44° x° A B C x° 7. Which of the following values is closest to zero? (A) 1 (B) 5 4 (C) 12 (D) 4 5 (E) 0:9 Grade 8 8. A jar contains 267 quarters. One quarter is worth $0.25. How many quarters must be added to the jar so that the total value of the quarters is $100.00? (A) 33 (B) 53 (C) 103 (D) 133 (E) 153 9. A package of 8 greeting cards comes with 10 envelopes. Kirra has 7 cards but no envelopes. What is the smallest number of packages that Kirra needs to buy to have more envelopes than cards? (A) 3 (B) 4 (C) 5 (D) 6 (E) 7 10. For the points in the diagram, which statement is true? (A) e > c (B) b < d (C) f > b (D) a < e (E) a > c y x (e, f ) (a, b) (c, d ) Part B: Each correct answer is worth 6. 11. The 26 letters of the English alphabet are listed in an in_nite, repeating loop: ABCDEFGHIJKLMNOPQRSTUVWXY ZABC : : : What is the 258th letter in this sequence? (A) V (B) W (C) X (D) Y (E) Z 12. A public holiday is always celebrated on the third Wednesday of a certain month. In that month, the holiday cannot occur on which of the following days? (A) 16th (B) 22nd (C) 18th (D) 19th (E) 21st 13. A circular spinner is divided into three sections. An arrow is attached to the centre of the spinner. The arrow is spun once. The probability that the arrow stops on the largest section is 50%. The probability it stops on the next largest section is 1 in 3. The probability it stops on the smallest section is (A) 1 4 (B) 2 5 (C) 1 6 (D) 2 7 (E) 3 10 14. A positive number is divisible by both 3 and 4. The tens digit is greater than the ones digit. How many positive two-digit numbers have this property? (A) 4 (B) 5 (C) 6 (D) 7 (E) 8 15. A rectangular pool measures 20 m by 8 m. There is a 1 m wide walkway around the outside of the pool, as shown by the shaded region. The area of the walkway is (A) 56 m2 (B) 60 m2 (C) 29 m2 (D) 52 m2 (E) 50 m2 20 m 8 m 1 m Grade 8 16. The results of asking 50 students if they participate in music or sports are shown in the Venn diagram. What percentage of the 50 students do not participate in music and do not participate in sports? (A) 0% (B) 80% (C) 20% (D) 70% (E) 40% Music Sports 15 5 20 17. There are 2 3 as many golf balls in Bin F as in Bin G. If there are a total of 150 golf balls, how many fewer golf balls are in Bin F than in Bin G? (A) 15 (B) 30 (C) 50 (D) 60 (E) 90 18. In the sequence shown, Figure 1 is formed using 7 squares. Each _gure after Figure 1 has 5 more squares than the previous _gure. What _gure has 2022 squares? (A) Figure 400 (B) Figure 402 (C) Figure 404 (D) Figure 406 (E) Figure 408 Figure 1 Figure 2 Figure 3 19. Mateo's 300 km trip from Edmonton to Calgary passed through Red Deer. Mateo started in Edmonton at 7 a.m. and drove until stopping for a 40 minute break in Red Deer. Mateo arrived in Calgary at 11 a.m. Not including the break, what was his average speed for the trip? (A) 83 km/h (B) 94 km/h (C) 90 km/h (D) 95 km/h (E) 64 km/h 20. Equilateral triangle ABC has sides of length 4. The midpoint of BC is D, and the midpoint of AD is E. The value of EC2 is (A) 7 (B) 6 (C) 6:25 (D) 8 (E) 10 Part C: Each correct answer is worth 8. 21. The positive factors of 6 are 1, 2, 3, and 6. There are two perfect squares less than 100 that have exactly _ve positive factors. What is the sum of these two perfect squares? (A) 177 (B) 80 (C) 145 (D) 52 (E) 97 22. In the list p; q; r; s; t; u; v, each letter represents a positive integer. The sum of the values of each group of three consecutive letters in the list is 35. If q + u = 15, then p + q + r + s + t + u + v is (A) 85 (B) 70 (C) 80 (D) 90 (E) 75 Grade 8 23. The net shown is folded to form a cube. An ant walks from face to face on the cube, visiting each face exactly once. For example, ABCFED and ABCEFD are two possible orders of faces the ant visits. If the ant starts at A, how many possible orders are there? (A) 24 (B) 48 (C) 32 (D) 30 (E) 40 A D B C E F 24. The number 385 is an example of a three-digit number for which one of the digits is the sum of the other two digits. How many numbers between 100 and 999 have this property? (A) 144 (B) 126 (C) 108 (D) 234 (E) 64 25. Student A, Student B, and Student C have been hired to help scientists develop a new avour of juice. There are 4200 samples to test. Each sample either contains blueberry or does not. Each student is asked to taste each sample and report whether or not they think it contains blueberry. Student A reports correctly on exactly 90% of the samples containing blueberry and reports correctly on exactly 88% of the samples that do not contain blueberry. The results for all three students are shown below. Student A Student B Student C Percentage correct on samples 90% 98% (2m)% containing blueberry Percentage correct on samples 88% 86% (4m)% not containing blueberry Student B reports 315 more samples as containing blueberry than Student A. For some positive integers m, the total number of samples that the three students report as containing blueberry is equal to a multiple of 5 between 8000 and 9000. The sum of all such values of m is (A) 45 (B) 36 (C) 24 (D) 27 (E) 29THE FIDE LAWS OF CHESS. Introduction FIDE Laws of Chess cover over-the-board play. The Laws of Chess have two parts: 1. Basic Rules of Play and 2. Competitive Rules of Play. The English text is the authentic version of the Laws of Chess (which were adopted at the 93rd FIDE Congress at Chennai, India) coming into force on 1 January 2023. Preface. The Laws of Chess cannot cover all possible situations that may arise during a game, nor can they regulate all administrative questions. Where cases are not precisely regulated by an Article of the Laws, it should be possible to reach a correct decision by studying analogous situations which are regulated in the Laws. The Laws assume that arbiters have the necessary competence, sound judgement and absolute objectivity. Too detailed a rule might deprive the arbiter of his/her freedom of judgement and thus prevent him/her from finding a solution to a problem dictated by fairness, logic and special factors. FIDE appeals to all chess players and federations to accept this view. A necessary condition for a game to be rated by FIDE is that it shall be played according to the FIDE Laws of Chess. It is recommended that competitive games not rated by FIDE be played according to the FIDE Laws of Chess. Member federations may ask FIDE to give a ruling on matters relating to the Laws of Chess. BASIC RULES OF PLAY. Article 1: The Nature and Objectives of the Game of Chess 1.1 1.2 1.3 1.4 The game of chess is played between two opponents who move their pieces on a square board called a ‘chessboard’. The player with the light-coloured pieces (White) makes the first move, then the players move alternately, with the player with the dark-coloured pieces (Black) making the next move. A player is said to ‘have the move’ when his/her opponent’s move has been ‘made’. The objective of each player is to place the opponent’s king ‘under attack’ in such a way that the opponent has no legal move. 1.4.1 The player who achieves this goal is said to have ‘checkmated’ the opponent’s king and to have won the game. Leaving one’s own king under attack, exposing one’s own king to attack and also ’capturing’ the opponent’s king is not allowed. 1.4.2 The opponent whose king has been checkmated has lost the game. 1.5 If the position is such that neither player can possibly checkmate the opponent’s king, the game is drawn (see Article 5.2.2). Article 2: The Initial Position of the Pieces on the Chessboard 2.1 2.2 The chessboard is composed of an 8 x 8 grid of 64 equal squares alternately light (the ‘white’ squares) and dark (the ‘black’ squares). The chessboard is placed between the players in such a way that the near corner square to the right of the player is white. At the beginning of the game White has 16 light-coloured pieces (the ‘white’ pieces); Black has 16 dark-coloured pieces (the ‘black’ pieces). These pieces are as follows: A white king usually indicated by the symbol K A white queen Two white rooks Two white bishops Two white knights Eight white pawns A black king A black queen Two black rooks Two black bishops Two black knights Eight black pawns usually indicated by the symbol Q usually indicated by the symbol R usually indicated by the symbol B usually indicated by the symbol N usually indicated by the symbol usually indicated by the symbol K usually indicated by the symbol Q usually indicated by the symbol R usually indicated by the symbol B usually indicated by the symbol N usually indicated by the symbol Staunton Pieces p Q K B N R 9 2.3 The initial position of the pieces on the chessboard is as follows: 2.4 The eight vertical columns of squares are called ‘files’. The eight horizontal rows of squares are called ‘ranks’. A straight line of squares of the same colour, running from one edge of the board to an adjacent edge, is called a ‘diagonal’. Article 3: The Moves of the Pieces 3.1 It is not permitted to move a piece to a square occupied by a piece of the same colour. 3.1.1 If a piece moves to a square occupied by an opponent’s piece the latter is captured and removed from the chessboard as part of the same move. 3.1.2 A piece is said to attack an opponent’s piece if the piece could make a capture on that square according to Articles 3.2 to 3.8. 3.1.3 A piece is considered to attack a square even if this piece is constrained from moving to that square because it would then leave or place the king of its own colour under attack. 3.2 The bishop may move to any square along a diagonal on which it stands. 3.3 The rook may move to any square along the file or the rank on which it stands. 3.4 The queen may move to any square along the file, the rank or a diagonal on which it stands. 3.5 3.6 3.7 When making these moves, the bishop, rook or queen may not move over any intervening pieces. The knight may move to one of the squares nearest to that on which it stands but not on the same rank, file or diagonal. 3.7 When making these moves, the bishop, rook or queen may not move over any intervening pieces. The knight may move to one of the squares nearest to that on which it stands but not on the same rank, file or diagonal. The pawn: 3.7.1 The pawn may move forward to the square immediately in front of it on the same file, provided that this square is unoccupied, or 3.7.2 on its first move the pawn may move as in 3.7.1 or alternatively it may advance two squares along the same file, provided that both squares are unoccupied, or 3.7.3 the pawn may move to a square occupied by an opponent’s piece diagonally in front of it on an adjacent file, capturing that piece. 3.7.3.1 A pawn occupying a square on the same rank as and on an adjacent file to an opponent’s pawn which has just advanced two squares in one move from its original square may capture this opponent’s pawn as though the latter had been moved only one square. 3.7.3.2 This capture is only legal on the move following this advance and is called an ‘en passant’ capture. 3.7.3.3 When a player, having the move, plays a pawn to the rank furthest from its starting position, he/she must exchange that pawn as part of the same move for a new queen, rook, bishop or knight of the same colour on the intended square of arrival. This is called the square of ‘promotion’. 3.7.3.4 The player's choice is not restricted to pieces that have been captured previously. 3.7.3.5 This exchange of a pawn for another piece is called promotion, and the effect of the new piece is immediate. 3.8 There are two different ways of moving the king: 3.8.1 by moving to an adjoining square. 3.8.2 by ‘castling’. This is a move of the king and either rook of the same colour along the player’s first rank, counting as a single move of the king and executed as follows: the king is transferred from its original square two squares towards the rook on its original square, then that rook is transferred to the square the king has just crossed. 3.8.2.1 The right to castle has been lost: 3.8.2.1.1 If the king has already moved, or 3.8.2.1.2 With a rook that has already moved. 3.8.2.2 Castling is prevented temporarily: 3.8.2.2.1 if the square on which the king stands, or the square which it must cross, or the square which it is to occupy, is attacked by one or more of the opponent's pieces, or 3.8.2.2.2 if there is any piece between the king and the rook with which castling is to be effected. 3.9 The king in check: 3.9.1 The king is said to be 'in check' if it is attacked by one or more of the opponent's pieces, even if such pieces are constrained from moving to the square occupied by the king because they would then leave or place their own king in check. 3.9.2 No piece can be moved that will either expose the king of the same colour to check or leave that king in check. 3.10 Legal and illegal moves; illegal positions: 3.10.1 A move is legal when all the relevant requirements of Articles 3.1 – 3.9 have been fulfilled. 3.10.2 A move is illegal when it fails to meet the relevant requirements of Articles 3.1 –3.9. 3.10.3 A position is illegal when it cannot have been reached by any series of legal moves. Article 4: The Act of Moving the Pieces 4.1 4.2 Each move must be played with one hand only. Adjusting the pieces or other physical contact with a piece: 4.2.1 Only the player having the move may adjust one or more pieces on their squares, provided that he/she first expresses his/her intention (for example by saying “j’adoube” or “I adjust”). 4.2.2 Any other physical contact with a piece, except for clearly accidental contact, shall be considered to be intent. 4.3 Except as provided in Article 4.2.1, if the player having the move touches on the chessboard, with the intention of moving or capturing: 4.3.1 one or more of his/her own pieces, he/she must move the first piece touched that can be moved. 4.3.2 one or more of his/her opponent’s pieces, he/she must capture the first piece touched that can be captured. 4.3.3 one or more pieces of each colour, he/she must capture the first touched opponent’s piece with his/her first touched piece or, if this is illegal, move or capture the first piece touched that can be moved or captured. If it is unclear whether the player’s own piece or his/her opponent’s was touched first, the player’s own piece shall be considered to have been touched before his/her opponent’s. 4.4 If a player having the move: 4.4.1 touches his/her king and a rook he/she must castle on that side if it is legal to do so 4.4.2 deliberately touches a rook and then his/her king he/she is not allowed to castle on that side on that move and the situation shall be governed by Article 4.3.1. 4.4.3 intending to castle, touches the king and then a rook, but castling with this rook is illegal, the player must make another legal move with his/her king (which may include castling with the other rook). If the king has no legal move, the player is free to make any legal move. 4.4.4 promotes a pawn, the choice of the piece is finalised when the piece has touched the square of promotion. 4.5 4.6 If none of the pieces touched in accordance with Article 4.3 or Article 4.4 can be moved or captured, the player may make any legal move. The act of promotion may be performed in various ways: 4.6.1 the pawn does not have to be placed on the square of arrival. 4.6.2 removing the pawn and putting the new piece on the square of promotion may occur in any order. 4.6.3 If an opponent’s piece stands on the square of promotion, it must be captured. 4.7 When, as a legal move or part of a legal move, a piece has been released on a square, it cannot be moved to another square on this move. The move is considered to have been made in the case of: 4.7.1 A capture, when the captured piece has been removed from the chessboard and the player, having placed his/her own piece on its new square, has released this capturing piece from his/her hand. 4.7.2 Castling, when the player's hand has released the rook on the square previously crossed by the king. When the player has released the king from his/her hand, the move is not yet made, but the player no longer has the right to make any move other than castling on that side, if this is legal. If castling on this side is illegal, the player must make another legal move with his/her king (which may include castling with the other rook). If the king has no legal move, the player is free to make any legal move. 4.7.3 Promotion, when the player's hand has released the new piece on the square of promotion and the pawn has been removed from the board. 4.8 4.9 A player forfeits his/her right to claim against his/her opponent’s violation of Articles 4.1 – 4.7 once the player touches a piece with the intention of moving or capturing it. 4.8. A player forfeits his/her right to claim against his/her opponent’s violation of Articles 4.1 – 4.7 .4.9. If a player is unable to move the pieces, an assistant, who shall be acceptable to the arbiter, may be provided by the player to perform this operation. Article 5: The Completion of the Game 5.1.1 The game is won by the player who has checkmated his/her opponent’s king. This immediately ends the game, provided that the move producing the checkmate position was in accordance with Article 3 and Articles 4.2 – 4.7. 5.1.2 The game is lost by the player who declares he/she resigns (this immediately ends the game), unless the position is such that the opponent cannot checkmate the player’s king by any possible series of legal moves. In this case the result of the game is a draw. 5.2.1 The game is drawn when the player to move has no legal move and his/her king is not in check. The game is said to end in ‘stalemate’. This immediately ends the game, provided that the move producing the stalemate position was in accordance with Article 3 and Articles 4.2 – 4.7. 5.2.2 The game is drawn when a position has arisen in which neither player can checkmate the opponent’s king with any series of legal moves. The game is said to end in a ‘dead position’. This immediately ends the game, provided that the move producing the position was in accordance with Article 3 and Articles 4.2 – 4.7. 5.2.3 The game is drawn upon agreement between the two players during the game, provided both players have made at least one move. This immediately ends the game. COMPETITIVE RULES OF PLAY Article 6: The Chessclock 6.1 ‘Chessclock’ means a clock with two time displays, connected to each other in such a way that only one of them can run at a time. ‘Clock’ in the Laws of Chess means one of the two time displays. Each time display has a ‘flag’. ‘Flag-fall’ means the expiration of the allotted time for a player. 6.2 Handling the chessclock: 6.2.1 During the game each player, having made his/her move on the chessboard, shall pause his/her own clock and start his/her opponent’s clock (that is to say, he/she shall press his/her clock). This “completes” the move. A move is also completed if: 6.2.1.1 6.2.1.2 the move ends the game (see Articles 5.1.1, 5.2.1, 5.2.2, 9.2.1, 9.6.1 and 9.6.2), or the player has made his/her next move, when his/her previous move was not completed. 6.2.2 A player must be allowed to pause his/her clock after making his/her move, even after the opponent has made his/her next move. The time between making the move on the chessboard and pressing the clock is regarded as part of the time allotted to the player. 6.2.3 A player must press his/her clock with the same hand with which he/she made his/her move. It is forbidden for a player to keep his/her finger on the clock or to ‘hover’ over it. 6.2.4 The players must handle the chessclock properly. It is forbidden to press it forcibly, to pick it up, to press the clock before moving or to knock it over. Improper clock handling shall be penalised in accordance with Article 12.9. 6.2.5 6.2.6 Only the player whose clock is running is allowed to adjust the pieces. If a player is unable to use the clock, an assistant, who must be acceptable to the arbiter, may be provided by the player to perform this operation. His/Her clock shall be adjusted by the arbiter in an equitable way. This adjustment of the clock shall not apply to the clock of a player with a disability. 6.3 Allotted time: 6.3.1 When using a chessclock, each player must complete a minimum number of moves or all moves in an allotted period of time including any additional amount of time added with each move. All these must be specified in advance. 6.3.2 The time saved by a player during one period is added to his/her time available for the next period, where applicable. In the time-delay mode both players receive an allotted ‘main thinking time’. Each player also receives a ‘fixed extra time’ with every move. The countdown of the main thinking time only commences after the fixed extra time has expired. Provided the player presses his/her clock before the expiration of the fixed extra time, the main thinking time does not change, irrespective of the proportion of the fixed extra time used. 6.4 Immediately after a flag falls, the requirements of Article 6.3.1 must be checked. 6.5 Before the start of the game the arbiter shall decide where the chessclock is placed. 6.6 At the time determined for the start of the game White’s clock is started.6.7. Default time: 6.7.1 The regulations of an event shall specify a default time in advance. If the default time is not specified, then it is zero. Any player who arrives at the chessboard after the default time shall lose the game unless the arbiter decides otherwise. 6.7.2 If the regulations of an event specify that the default time is not zero and if neither player is present initially, White shall lose all the time that elapses until he/she arrives, unless the regulations of an event specify, or the arbiter decides otherwise. 6.8 A flag is considered to have fallen when the arbiter observes the fact or when either player has made a valid claim to that effect. 6.9 Except where one of Articles 5.1.1, 5.1.2, 5.2.1, 5.2.2, 5.2.3 applies, if a player does not complete the prescribed number of moves in the allotted time, the game is lost by that player. However, the game is drawn if the position is such that the opponent cannot checkmate the player’s king by any possible series of legal moves. 6.10 Chessclock setting: 6.10.1 Every indication given by the chessclock is considered to be conclusive in the absence of any evident defect. A chessclock with an evident defect shall be replaced by the arbiter, who shall use his/her best judgement when determining the times to be shown on the replacement chessclock. 6.10.2 If during a game it is found that the setting of either or both clocks is incorrect, either player or the arbiter shall pause the chessclock immediately. The arbiter shall install the correct setting and adjust the times and move-counter, if necessary he/she shall use his/her best judgement when determining the clock settings. 6.11.1 If the game needs to be interrupted, the arbiter shall pause the chessclock. 6.11.2 A player may pause the chessclock only in order to seek the arbiter’s assistance, for example when promotion has taken place and the piece required is not available. 6.11.3 The arbiter shall decide when the game restarts. 6.11.4 If a player pauses the chessclock in order to seek the arbiter’s assistance, the arbiter shall determine whether the player had any valid reason for doing so. If the player has no valid reason for pausing the chessclock, the player shall be penalised in accordance with Article 12.9. 6.12.1 Screens, monitors, or demonstration boards showing the current position on the chessboard, the moves and the number of moves made/completed, and clocks which also show the number of moves, are allowed in the playing hall. 6.12.2 The player may not make a claim relying only on information shown in this manner. Received: 26 November 2019 Revised: 10 January 2020 Accepted: 19 January 2020 DOI: 10.1111/obr.13005 PEDIATRICS/PHYSIOLOGY Adipokines: A gear shift in puberty Desirée Nieuwenhuis | Natàlia Pujol-Gualdo Amanda J. Kiliaan Department of Anatomy, Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Preclinical Imaging Center PRIME, Nijmegen, The Netherlands Correspondence Amanda J. Kiliaan, PhD, Associate Professor, Department of Anatomy, Donders Institute for Brain, Cognition, and Behaviour, Preclinical Imaging Center PRIME, Radboud university medical center, 6500 HB Nijmegen, Geert Grooteplein 21N 6525 EZ Nijmegen, The Netherlands. Email: amanda.kiliaan@radboudumc.nl Funding information Europees Fonds voor Regionale Ontwikkeling (EFRO), Grant/Award Number: BriteN 2016 1 | INTRODUCTION The prevalence of obesity in adolescents and children is increasing in | Ilse A.C. Arnoldussen | Summary In this review, we discuss the role of adipokines in the onset of puberty in children with obesity during adrenarche and gonadarche and provide a clear and detailed overview of the biological processes of two major players, leptin and adiponectin. Adipokines, especially leptin and adiponectin, seem to induce an early onset of puberty in girls and boys with obesity by affecting the hypothalamic-pituitary- gonadal (HPG) axis. Moreover, adipokines and their receptors are expressed in the gonads, suggesting a role in sexual maturation and reproduction. All in all, adipokines may be a clue in understanding mechanisms underlying the onset of puberty in child- hood obesity and puberty onset variability. KEYWORDS adipokines, obesity, puberty 1,2 the age of 5 years were overweight or were with obesity in 2016, and 3 Obesity is defined by an excessive accumulation of white adipose tissue (WAT), and it is often indicated by a body mass index (BMI) 4 above 30. Two main types of adipose tissue were described: WAT and brown adipose tissue (BAT), which differ in morphology and func- 5-7 Ilse A.C. Arnoldussen and Amanda J. Kiliaan contributed equally to this work. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2020 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation Obesity Reviews. 2020;21:e13005. wileyonlinelibrary.com/journal/obr 1 of 10 https://doi.org/10.1111/obr.13005 alarming rates. Specifically, worldwide, 41 million children below this number is expected to increase to 70 million in 2025. obesity is associated with various severe health complications, includ- ing increased risk of diabetes mellitus type 2, hypertension, heart dis- eases, and disturbances in sex hormone levels. 5,6 and mitochondria and plays a role in thermogenesis. Adipocytes in tion. BAT consists of adipocytes containing multiple lipid droplets WAT contain only a few mitochondria and a single lipid droplet. Adipose tissue has several functions including the storage of energy, thermogenesis, and the production and secretion of adipokines Generally, two physiological processes, adrenarche and gonadarche, 11,24 Childhood 5,7,8 a key role in puberty onset. Puberty is known as a period through which the body changes physically, being a physiological process resulting in the maturation of children, i.e. they develop sexual characteristics and obtain reproduc- 9,11 Adipokines are involved in a number of physiological processes including blood pressure, metabo- lism, glucose, and vascular homeostasis and may play amongst others 8-10 (hormones, cytokines, and peptides). tive functions. between obesity and puberty,2,12-23 the biological mechanisms under- lying obesity and puberty onset remain unclear. Hereafter, we review in detail the role of adipokines in the onset of puberty in childhood obesity. Although many studies have shown associations 2 | INITIATION OF PUBERTY PHYSIOLOGICAL PROCESSES IN THE interact to regulate the onset of puberty. During adrenarche, the adrenal cortex secretes steroid hormones (including 2 of 10 NIEUWENHUIS ET AL. androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate (DHEAS), androstenedione, and cortisol), insulin-like growth factor, and growth hormone, which contribute to the pubertal insights on new genetic loci (e.g. melanocortin-4 receptor, mitochon- drial carrier 2, and mitogen-activated protein kinase 13) and on sev- eral pathways that regulate the timing of puberty; however, it partly 34 9,24,25 Both adrenarche and gonadarche are involved in the development growth spurt, body odor, skin oiliness, and skeletal maturation. explains puberty timing variation. Thereby, defining the role of 25 adipokines is of importance in elucidating the variability in puberty as the expression of adipokines is sex-specific and is altered with body composition, adiposity, and during growth spurts. Moreover, adipokines and their receptors are expressed in gonads and several brain regions suggesting involvement in the onset of puberty and sex- ual maturation. Lastly, adipokines interfere in processes regulating timing and duration of puberty, for instance in the HPA and HPG axes which are both key players during adrenarche and gonadarche. Involvement of adipokines in the onset of puberty and specifically in individuals with obesity will be further reviewed in the next 2,24 3 | Puberty onset in girls is assessed using different markers, such as thelarche (breast development), menarche (the start of of pubic hair. pituitary-gonadal (HPG) axis is activated,2,26 and several hormones have been identified to participate in the activation of the HPG axis During gonadarche (Figure 1), the hypothalamic- 2,27 Kisspeptin, neurokinin B, and dynorphin are released by specialized including kisspeptin, neurokinin B, dynorphin, leptin, and ghrelin. 28 key regulator of the pulsatile secretion of gonadotropin releasing neurons, the KNDy neurons in the hypothalamus. Kisspeptin is a 29,30 B stimulates, and dynorphin inhibits the release of kisspeptin, which hormone (GnRH) from the hypothalamus. In addition, neurokinin implies that both coordinate a pulsatile release of kisspeptin. 31 Sub- sections. sequently, the activated HPG axis induces the pituitary gland to secrete luteinising hormone (LH) and follicle stimulating hormone (FSH). As a result, gametogenesis occurs, and the gonads will release sex hormones. Consequently, secondary sex characteristics develop including breast development in girls and an increased testicular vol- 2,26,32 is possibly due to differences in levels of body fat, hypothalamic-pitui- THE ONSET OF PUBERTY IN GIRLS ume in boys. The age at puberty onset varies greatly among individuals, which 19 35 menstruation), and pubic hair development. 33 genome-wide association studies have provided important new tary-adrenal (HPA) axis activity, and genetic background. Recent The average age of However, this age differs between cultures and ethnicities, and since 1980, age at menarche is girls at start of menarche is 12.4 years. 36 significantly decreasing. 36-39 F I G U R E 1 Hormonal regulation in the initiation of puberty in boys and girls. The secretion of kisspeptin, neurokinin B, and dynorphin from KNDy neurons initiate the release of gonadotropin releasing hormone (GnRH) from the hypothalamus. This activates the pituitary gland to produce and secrete luteinising hormone (LH) and follicle stimulating hormone (FSH), which in turn stimulate the gonads to produce estrogen and testosterone in girls and boys, respectively 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License NIEUWENHUIS ET AL. 3 of 10 T A B L E 1 Summary of included studies Authors Year Country Study Design Primary Outcome Sex Sample Size (n) Age (y) Data Collection Lian et al21 2019 China Cross-sectional Puberty starts earlier in Chinese Han girls with obesity compared with Chinese Han girls with normal weight. Girls 2996 9-19 2012 and 2013 Biro et al12 Lazzeri et al20 2018 USA 2018 Italy Longitudinal Cross-sectional Body mass index had a greater effect on age at menarche than did race and ethnicity. Girls 946 6-16 2004-2014 Li et al23 2018 China Longitudinal For both, boys and girls, a higher BMI (ie, overweight and obese) is associated with earlier onset of puberty Girls Girls Boys Girls 542 Deng et al22 Flom et al15 2017 China Cross-sectional Increased BMI is associated with early timing spermarche and menarche. Boys Girls Girls 1278258 9-15 2005-2012 He et al24 Holmgren et al17 2017 China 2017 Sweden Cross-sectional Longitudinal Onset of puberty is not related to obesity in boys. Boys Boys Girls Girls 782 7-17 972 929 5839 Kelly et al19 2017 UK 2016 Brazil 2016 USA Longitudinal prospective cohort Higher BMI in girls is associated with the onset of menstruation at an earlier age. 11 10-18 11-17 Barcellos Gemelli et al25 Cross-sectional Longitudinal Excess weight is associated with early age of menarche. Girls 727 2014 2003-2009 Glass et al16 Lee et al26 In girls, but not in boys, greater adiposity is associated with the earlier onset of puberty. Boys Girls 135 Cabrera et al27 Leonibus et al14 2014 USA 2013 Italy Cross-sectional Longitudinal Thelarche occurred earlier than recently reported, while age of menarche remained unchanged. Girls 610 3-17.9 2007 2005-2012 Currie et al13 2012 Europe, USA, Canada Cross-sectional Overweight/obesity during childhood predicts the early onset of puberty in girls. Girls 20410 11, 13, 15 2005-2006 2017 USA Prospective birth cohort Overweight/obese status at the age of 7 ye was associated with increased risk of early menarche 788 From birth to menarche occurred Pregnancies 1959-1966 2016 USA Cross-sectional Boys with overweight enter puberty earlier compared with boys with normal weight or obesity, while puberty starts later in boys with obesity compared with boys with normal weight and overweight. Boys 3872 6-16 2005-2010 Overweight during childhood shows a relation with the early onset of puberty in girls. 6535 4259 695 11 15 5.8-12.2 2009/2010 2013/2014 2014-2017 Higher BMI during childhood is associated with early puberty. 2008 and 2009 2000-2002 Obesity during childhood is related to the earlier onset of puberty. Boys Girls 84 123 71 (Continues) 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 4 of 10 NIEUWENHUIS ET AL. 3.1 | Fat storage For the initiation of puberty, the timing of stimulation and/or inhibi- tion of different hormones is important, and additionally, a certain amount and distribution of body fat is needed in order to start menar- che, which emphasizes the importance of body fat. From an evolution- ary point of view, body fat increases in mammalian females during puberty onset, and it highlights the need to guarantee a healthy preg- 40 women with anorexia nervosa. particularly body fat localized predominantly on the gluteofemoral fat depots, is profoundly associated with start of menarche, more than nancy, offspring, and maternal survival. fat, sex-hormones, and neuroendocrine alterations can evolve in men- strual dysfunction, for instance, in women with severe obesity or in 41-43 44-46 to gluteofemoral fat depots suggesting that leptin may convey infor- amount of total body fat. mation on body fat distribution to the hypothalamus during puberty. An improper level of body Importantly, body fat distribution, Blood leptin levels are strongly related 45 3.2 | HPG axis The HPG axis is activated by the release of kisspeptin resulting in the release of GnRH from the hypothalamus, and LH and FSH from the pituitary gland. In girls, FSH is involved in the development of the folli- cles in the ovaries, and it promotes the secretion of estrogen. LH stim- ulates the production of androgen hormones and induces ovulation 48 9,47 the release of kisspeptin and neurokinin B, and kisspeptin thereby (Figure 1). The secretion of estrogen has an inhibitory effect on inhibits the GnRH release from the hypothalamus. pattern of GnRH is important for the regulation of the menstrual cycle. This roughly 28-day-cycle comprises several phases, including the follicular phase and luteal phase. During the follicular phase, increasing levels of FSH stimulate the maturation of follicles and the production of estrogen from the ovaries. This in turn inhibits the release of FSH from the pituitary gland. A high level of estrogen will induce the production of LH by the pituitary gland, resulting in ovula- tion. The matured follicle secretes progesterone thereby inhibiting the release of GnRH. When the corpus luteum is demolished, there is less 48 3.3 | Adipokines According to results from studies reported in Table 1, girls with obe- sity enter puberty earlier compared with girls with normal higher leptin concentrations inhibit the intake of food and increases inhibition of GnRH. As a consequence, the cycle will start again. whole process, starting from the activated HPG axis, results in the development of the secondary sex characteristics in girls including 9,47 thelarche and menarche. 13,14,16-23,49-51 weight. these girls might be found in the secretion of adipokines. For instance, leptin is positively associated with the amount of body fat. Generally, energy expenditure. 9,52-54 An explanation for the early onset of puberty in The expression This TABLE 1 (Continued) Authors Year Country Study Design Primary Outcome Sample Sex Size (n) Age (y) Data Collection Herman-Giddens et al28 2012 USA Cross-sectional Observed mean ages of beginning genital and pubic hair growth and early testicular volumes were earlier than in past studies, depending on the characteristic and race/ethnicity. Boys 4131 6-16 2005-2010 Sorensen et al29 Aksglaede et al30 2010 2009 Denmark Denmark Cross-sectional/longitudinal Longitudinal Puberty onset at earlier ages was associated with an increased BMI in boys. Boys 1528 5.8-19.9 1991-1993/2006-2008 1930-1969 Juul et al31 Ribeiro et al32 2007 2006 Denmark Portugal Retrospective cohort Cross-sectional Higher BMI is associated with early voice break. 11-15 10-15 1990-1999 Kaplowitz et al18 Abbreviation: BMI, body mass USA Cross-sectional The early onset of puberty in Caucasian girls is likely related to an increased BMI. 5-12 1992-1993 2001 index. The higher BMI in boys and girls at 7 y of age, the earlier they enter puberty. Boys 21 612 Girls 135 223 Boys 463 Boys 382 Girls 437 Girls 10 750 Early sexual maturation in boys and girls is associated with overweight. 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License NIEUWENHUIS ET AL. 5 of 10 Leptin may possibly play a role in adrenarche as its plasma level increases with higher levels of body fat and as it can modulate both girls. 33 ing adrenarche. In coherence, in children with obesity, the androgen These findings suggested that lower reproductive status was associated with higher total adiponectin concentrations and that a higher reproductive status was related to higher HMW adiponectin the HPA and HPG axes. These axes are functionally integrated dur- DHEAS was positively associated with leptin levels. Nevertheless, concentrations in girls. In addition, individuals with obesity often another study showed that enhanced adrenal androgen secretion in girls with premature adrenarche was not explained by leptin or BMI 55 ated with androgen levels in girls ; however, it was not related to levels. and IL-6. TNF-α alters, and IL-6 inhibits the expression of 56 8 In addition, the adipokine adiponectin was negatively associ- 57 differences of adiponectin seem to develop during the progression of 56 adiponectin (Figure 2). Thereby, a low level of total adiponectin and/or high levels of inflammatory cytokines in individuals with obe- sity can promote the onset of puberty. Many more adipokines are secreted by WAT including omentin, 52,65-67 9,36,62,68 adrenarche in girls with Prader-Willi syndrome. Interestingly, sex puberty. adrenarche; however, both are not required factors. Thus, leptin and adiponectin might be able to influence In gonadarche, leptin can stimulate the secretion of kisspeptin, and subsequently activation of the HPG axis, which eventually increases the expression of estrogen and androstenedione in the ova- 58 2,60 65-67 The expression of these ries (Figure 2). Ob gene in WAT, resulting in the synthesis and secretion of leptin. Thus, high levels of leptin promote onset of puberty in girls via secre- tion of kisspeptin, and estrogen stimulates leptin secretion addition- ally. Moreover, adiponectin can affect the HPG axis due to the expression of adiponectin receptors in the hypothalamus, pituitary In return, estrogen stimulates the expression of the 59 gland, and gonads. onset as it inhibits the secretion of kisspeptin and GnRH in the hypo- thalamus and the release of GH and LH in the pituitary gland, and 2,60-62 52,60 63 girls with central precocious puberty (CPP). Moreover, total adiponectin had negative correlations with progression of puberty in girls (defined by Tanner stages), whereas HMW adiponectin had FIGURE 2 Adipokinesaffectingthe initiation of puberty in girls. Leptin stimulates the release of kisspeptin in KNDy neurons, which activates the hypothalamus to produce gonadotropin releasing hormone (GnRH). In response to the release of GnRH, the pituitary gland secretes follicle stimulating hormone (FSH) and luteinising hormone (LH), which stimulates the ovaries to release estrogen resulting in the formation of secondary sex characteristics in girls. Estrogen stimulates the production of leptin. Adiponectin inhibits GnRH release resulting in reduced levels of GnRH and thereby a delayed onset of puberty. TNF- α and IL-6 inhibit the production of adiponectin and therefore stimulate the onset of puberty In detail, adiponectin is a regulator of puberty thereby inhibiting the onset of puberty (Figure 2). with obesity often have low levels of adiponectin. et al. showed that total adiponectin was significantly lower, whereas high molecular weight (HMW) adiponectin was significantly higher in ment. 55 63 develop a chronic low-grade inflammatory state, which can be indi- cated by a high level of circulating inflammatory cytokines like TNF-α 64 Individuals Sitticharoon positive associations with LH levels and the progression of puberty in 63 visfatin, resistin, and chemerin. and visfatin are expressed in the ovaries. adipokines in the ovaries suggests a role within the reproductive sys- tem; however, the exact biological processes have to be examined. Thus, specifically leptin, adiponectin, and inflammatory cytokines pro- duced by WAT could be permissive key players during an early onset of puberty in girls with obesity. As an exception, HMW adiponectin seems to have a stimulatory effect on peripheral repro- ductive function as HMW is not able to cross the blood brain 63 barrier. 4 | Markers that are used to assess puberty onset in boys are THE ONSET OF PUBERTY IN BOYS spermarche, voice break, testicular volume, and pubic hair develop- 35 spermarche develop in the early stages of puberty onset, voice In women, omentin, chemerin, While pubic hair development, larger testicular volume, and 69 testicular volume increases, which occurs at an average age of break usually appears in later stages of puberty. Generally, first 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 6 of 10 NIEUWENHUIS ET AL. 11.9 years, followed by the development of pubic hair at 12.2 years of average, and lastly, boys experience spermarche around an aver- 55 related with leptin levels. Thereby, leptin plausibly has a minor impact in adrenarche in boys. Since leptin receptors are found in the hypothalamus, pituitary gland, and testes, they might be involved in the onset of puberty by affecting the HPG axis during gonadarche. Leptin stimulates the release of kisspeptin and GnRH, and as a consequence, it accelerates the onset of puberty (Table 1, Figure 3). In contrast, adiponectin inhibits the secretion of GnRH, GH, LH, and FSH therewith delaying the onset of puberty. However, adiponectin levels are generally lower in men compared with women and even lower in men with obe- age age of 13.4 years. 70 4.1 | Fat storage Many aspects of the reproductive physiology are energetically demanding,71 and therefore, an adequate energy level is necessary. In boys, a dynamic change in body composition occurs around the age of 10 to 13 years, in which they gain approximately 40% of sity. culating inflammatory cytokines. levels can stimulate the HPG axis and therewith an early onset of puberty in boys. Nevertheless, leptin can inhibit the production of tes- 72 mostly consisting of lean mass, which causes exhaustion of most of fat. Subsequently, a growth spurt follows in which they gain tissue 72 in boys, an adequate amount of body fat is important in the onset of their body fat. These alterations in amount of body fat indicate that 4.2 | Puberty in boys is initiated by the release of kisspeptin. As mentioned before, this activates the HPG axis, resulting in the release of GnRH from the hypothalamus, and consequently the release of LH and FSH 9,74 puberty. tosterone from the testes, to estrogen (Figure 3). of the development of secondary sex characteristics in boys. Additionally, leptin can affect fertility in men as it can modulate the nutritional support of spermatogenesis, and moreover, dysfunction of spermatogenesis is associated with an increased leptin level and 73 58 2,60-62 HPG axis from the pituitary gland (Figure 1). and LH stimulates the secretion of testosterone from the testes, which inhibits the release of kisspeptin from the KNDy neurons and 9,48 in men, the release of kisspeptin is more consistent, causing a con- 29,48 subsequently GnRH from the hypothalamus. receptors expressed on KNDy neurons. In humans, KNDy neurons Contrarily to women, LH-induced testosterone levels lead to the stant release of LH. development of secondary sex characteristics in boys. differences between sexes in kisspeptin release are related to a sex- specific and sex steroid-dependent kisspeptin system as estrogen and progesterone modulate kisspeptin activity through the sex-steroid 48 in the infundibular nucleus are involved in negative and positive sex- 48 tal exposure to sex steroids and result in sex-specific differences in steroid feedbacks. kisspeptin release. These sexual dimorphisms are induced by perina- 75,76 4.3 | Adipokines The association between obesity and puberty onset in boys is rather controversial compared with findings in girls. Most studies reported an early onset of puberty in boys associated with increased ate adipose tissue from actual breast tissue. stages are more difficult to assess than female stages as boys lack a more determined marker such as menarche. Thirdly, puberty onset can be indicated by the activation of the HPG axis, and the presence of these secondary sex characteristics is the result of hormonal 2 14,17,22,23,50,51,77,78 BMI, 20,49 all while others reported no associations at Current markers used 79 16,80 or a delayed onset of puberty (Table 1). The presence of excessive adipose tissue can be involved in puberty onset in boys as the secretion of adipokines can modulate both adrenarche and gonadarche. Leptin can affect adrenarche by modulating both the HPG and HPA axes,33 and moreover, androgen levels were positively 55 nal androgen secretion in boys with premature adrenarche was not associated with plasma leptin levels. Nevertheless, enhanced adre- 9 In more detail, 61,62 adiponectin, and individuals with obesity often have high levels of cir- Moreover, inflammatory cytokines, TNF-α, and IL-6, inhibit expression of the leptin receptor in the testis. FSH induces spermatogenesis, too. function and role still have to be examined. 64 High leptin and low adiponectin and fat tissue can convert testosterone Both processes might result in the delay 29,61,79 81,82 In men, other adipokines like chemerin are found in the gonads 65 Thus, particularly high leptin and low adiponectin levels stimulate the HPG axis and thereby accelerate the onset of puberty in boys. Additionally, leptin can dysregulate the development of secondary sex characteristics and spermatogenesis by affecting testosterone levels and nutritional sup- port of spermatogenesis. 5 | LIMITATIONS AND FUTURE RESEARCH DIRECTIONS Even though multiple epidemiological studies have shown the link between puberty onset and obesity, there are some important limita- tions. Firstly, determining both the onset and stage of puberty is rather difficult. For instance, assessing the stage of breast develop- ment in girls with obesity is complicated as clinicians should differenti- 2 changes in response to the activated HPG axis. to determine the onset of puberty refer to secondary sex characteris- tics, such as testicular volume in boys and breast development in girls. A more accurate measurement of puberty onset would be to combine secondary sex characteristics with plasma or serum hormone level measurements such as LH, FSH, adipokines, e.g. leptin. Thereby, differences in puberty measurements could explain variations in the age of puberty onset between boys and girls within different Thereby, resistin is expressed in the testes of rats, but its exact 83 Secondly, male pubertal 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License NIEUWENHUIS ET AL. 7 of 10 FIGURE 3 Adipokines affecting the initiation of puberty in boys. Leptin activates kisspeptin secretion in KNDy neurons, this activates the production of gonadotropin releasing hormone (GnRH) from the hypothalamus. GnRH stimulates the pituitary gland to secrete follicle stimulating hormone (FSH) and luteinising hormone (LH), activating the production of testosterone from the testes allowing the development of secondary sex characteristics. Leptin also inhibits the production of testosterone, which may cause a delayed onset of puberty. Adiponectin inhibits GnRH release. Low levels of adiponectin, as a result of TNF-α and IL-6 expression, lead to a reduced inhibition of GnRH. In response to GnRH release, the pituitary gland will secrete FSH and LH, and the testes will produce testosterone resulting in the development of secondary sex characteristics in boys countries, and In addition, the inclusion of a of puberty. ferent time points is complicated, as subjects examined several decades ago presented pronounced differences concerning lifestyle patterns such as nutrition and exercise habits. Lastly, obesity or over- weight is often determined by BMI, a classification based on weight and height measurements. Additionally, it is important that all studies studies or across continents, ethnicities proper age range (8-16 years) is important when assessing the onset (Figure 4). 12-15,17,20-23,49,77-79,84,85 30,47 Furthermore, comparison between studies from dif- 86 Specifically in children, BMI is often dependent on age and growth use the same anthropometric standards and sex-specific cut-offs. 13,14,16-23,49-51,77-80 fat and would represent a more accurate measurement in its regard. Based on this review, several suggestions can be made for further research. Firstly, the roles of adipokines like resistin, chemerin, visfatin, and omentin in puberty onset, fertility, and sexual maturation should be examined in detail. Secondly, future research examining the onset of puberty should combine indicators of puberty onset (e.g. breast development or testicular volume) with plasma or serum hor- mone measurements such as LH, FSH, sex-steroids, adipokines (e.g. spurts. ment in case of growth spurts. distribution of body fat should be taken into account in determining puberty and obesity in children. For instance, the body adiposity index (BAI), which was introduced in 2011 by Bergman et al.,87 uses hip cir- cumference and height in order to estimate the percentage of body 87 Thereby, BMI is a less accurate measure- F I G U R E 4 87,88 Therefore, both percentage and Average age of puberty onset in Europe, China, and the United States according to several studies from Table 1. Age of puberty onset ranges from 8.47 to 13.33 years in girls and from 8.63 leptin), and body fat distribution (e.g. BAI,87 waist-hip ratio's and/or dual-energy X-ray absorptiometry (DXA)2). Additionally, defining con- sistent and general measurements of puberty in both boys and girls, combined with a proper age range (8-16 years), would facilitate the comparisons between different studies and their results. 12-15, 17, 20-23, 25-29, 31 to 13.7 years in boys. included if average age of markers used to assess puberty was not reported. Pink: girls. Blue: boys Studies (Table 1) were not 39, 56 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 8 of 10 NIEUWENHUIS ET AL. 6 | CONCLUSION In conclusion, epidemiological data regarding obesity and puberty onset in girls show similar outcomes as adiposity results in the early onset of puberty in girls. The majority of the studies examining boys with obesity indicate an early onset of puberty, while not all reported an earlier onset of puberty. In detail, high leptin, TNF-α, and IL-6 levels combined with low adiponectin levels stimulate the activation of the HPG axis in girls and boys with obesity, and 5, 45, 50, 51 REFERENCES 1. Kumar S, Kelly AS. Review of childhood obesity: from epidemiology, etiology, and comorbidities to clinical assessment and treatment. May- o Clin Proc. 2017;92(2):251-265. 2. Reinehr T, Roth CL. Is there a causal relationship between obesity and puberty? The Lancet Child & adolescent health. 2019;3(1):44-54. 3. WorldHealthOrganization. Facts and figures on childhood obesity. 2017. 4. Guglielmi V, Sbraccia P. Obesity phenotypes: depot-differences in adipose tissue and their clinical implications. Eat Weight Disord. 2018; 23(1):3-14. 5. Gomez-Hernandez A, Beneit N, Diaz-Castroverde S. Escribano O. 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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. 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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 goverSTARS 1 LETTERS Q-RSTARS 1 LETTERS P+Q+R