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R or H?
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Eff..rs of ott.-PoFllat i What woLrld hoppen ro our colnrry i, it is ovetsp.pulored? When our counrry is ov€.-populdted, re @ €xp€ri.nce rh€ foll.wirg: Food is our bdsic h@d. Wh€n th€.Cs an ih.re.se ir populdtion it neans thar hore ,@d is iealed. It rheds ho .naJgh food, rrtrple irll srruggle wirh eddr oth€r in ordeLro €!'r- As o l!fllr, lhde rill be o f@d -- , ond ou, now]nert of on ihdiyiduol fron d c..tair - the move$eni o, on individudl our of o cerrain pla.e which help r€duce ihe populotion of th6t fr Arcih€. b.sic ned is w.ra. Wde. shorroge ocu.s when there is on ircreare of hu,nber of p@ple ro be $pptied. rn owr-popur.t d ore.s, woler is rdior€d, Ir rEB rhoi supplies like ti,tWSS ond ,IWSI can'i $pply enoish worer. Do you hdve enough supply of sai.. in your oreo? Aside f.om food alld worer, shelier is olso ohe o, our inportant heeds. As the populoiion ihcre.!e!, building n.w hoLr!€s or rhelt€r is limit.i. To find solulion to this prcbl€n, some goverihent og.ncies dnd orhs non{ov€Ihrehl offi.iofs (N6O) .onvefied sot@ ti.elields, du,np site. dnd nountcirlr inlo flbdivisions dnd relidentiols. Sut whot uould be ths effect o{ coMrtiig .i@fields to .6id€nri6l uits in our food supply? z , 2 Z Z :'", becouse there ore no enough space for prcpex garbage dkposol. ^s o r€sulr, sore peoPle lend to ihrow'their gorbdge onywh.f€. oorbdge baones brc{niry ond rursing ground of iEecrs and onidols ihot @se horm ro pe.ple. Dec.yiry garboge olso produces r,hpleaiant odor ard ehen burn if pmduces pois.nour qds @lled nelhohe As ihe populdtion incr€a3*, the 9d6.9e dso incraes. nris is T't ,,8 T H Wha you de living in on oa-populdi.d pla@, you moy oqaiae halrh prcblerns. Ir is be@@. the woi.r srpply is limit.d ihct will l..d you to poor hygi.ni. hobirs. In plo.4 like rhis, the surrouhdiigs naybe uniidy. o focrorthoi @uld oko cfFe.t your h4l'th. The common oilments rhot yd @uld oc$rire in ovesfDpllar€d ploces ore bEnchil is, o5l hnq. diqrrha and rube.culosis. 7,\ ,\\ \1" 6. Lnck of Herlrh sarvice llosi Pelple in 6n oM-populci€d 6ra 90 ro rubli. heilrh @trtas ond governhent hospirols be6u.e ii prcvides fr@ @Eulrorion oid los @sr rEdicdrions. A3 a ..suli, lh€s€ gow.nnenr dg€rciB b.@ne itud.4$re in mcetiig ihe n eds b..ou!€ df ihsrffici€nr funds. Lock of medicol personnel ,o odmaiisi€I is also s problen in mosr hosptols ev€n rhere or. od.audtc supply of hedicire!. 7_ Do you how wlry rhe crim€ roi€ hexs ih becdur€ fiDre pe.ple o.e fnJrrct€d d@ ro sLffici€.i naE io supp.rr their forniliG. ouf country inclY{ses? If is uh.mploym€ni dnd hdve no arinet .re u$dv gr€{rer ia dn dq-popltdled ra whq. tl, , a, v, tlr I E. Air ard Wat€r Pollutioh How dir be.o'nes pollut€d? I11€ dir b@'n€s p.llurn be.4ne of rhe hormfolgoees thot ser. produ.4 by the fdciori€s and vehicles. Itete {octories ond whi.l6 @ fuel ro run nochiB ond .JBin6. In ,h€ prc.ess, they give our Cdrboh Dioxide ond other ho.6ful gars.r such 6 Nittugei Oxide, Corbon l oioxide dnd Le.d iiio the oir. Do you know whot .ontdbute io ihe incr€asing number of whides qnd foctories? It is ihe inc.6e o, populdtion. As whdt I hove dis.!sse!, wirh a lihired sra.e 9@bd9e disposalie one of the problens thot .o!ld ise i, dh o!er-pop!,.t€d ploce. exn,jple ot thie orc rhos€ pelpl€ livi,rg oh the raverside teid 'ro ,hrou, lheir gEr&ge Hde you seen 'th. P6si9 river or the Tulyahan river? Did you {ind it Whdr do you think i! ihe eff€.t of ihis ih the.re4iures sho lives ih Ahothd f6do.s thal could.on rlbule to wdtd pollutioh dre oil s?ills, gorbqg€ fro,n boa, or ships ahd som€ ihdust.iol wosre. 9. Ite l@96f p4.enroge group. Individuols who orc this grclp. of olr popllarioh is compos.n of the working @pobla of s'rpporting ,heir fomilies nok !-up Though rhas group hol& the lojgeei percenroge of d. populaiion, rhis olso becomer one o{ oveFpopulored probl€]ns b€4use there ore rc jobs awildble fo. oll of iha10. Erergy Shortdge ltere will be on energy shortdge iJ ihe populdtion incre63"l be.dise rhe d.,nand i. €le.iriciry is high. Why is thai wh.n th. PoPqldion inclE.g, rhe d4ord in el4tricity is high? Ir B be.ouse there $,ould be 8to.e hdsat dnd blildirys to lighr ond nore el?riric oPPliohces ro run. rt.6rcznho!3.Ef+ed Whor is rhe grernho@ eff€.r? In whoi say il c.uld offect c2 6re.hhG. effed is rhe wdrniltg of rhe drltlosphee. lvhen the 5un worft rhe.nrrh s1jrf.@, sone of rhe h@r go€J bo.k ro rhe ornos?herc. Air an the dtnDsphere which is C@boi Dioxid. ,rops ihe heot 6hd it mok6 the a.th very worm. As ihe populdtion coniinuou!|,l gtol4 , the gt@rl$use etfe.t b@res no.e visible. Ir is becaosu ,hera ore mo.e focrories snd whicl.s iha, produce wdst€s ond fuma5 which cduses more C{.bo. Diodde ir the ormosphere. As a rcsutt, ,herc eiould be nore h4, ,rop in the ornosphere uhich osk6 th. @ih nuch wornerIf this will hoppen continuously, ,h€ fish ih th€ ocah *ill di€, ricerields/f@mlands will dry too due to lh€ wcm clitnole 12. Destruction of rhe Ozone Loyer A5 whot you hove l@med lrheh you de in v5-6, rhot the qzore ldver is 'the proiecrive loy€. of the olnosPhd€. ft protects us {rom the homful effects of ultrdviolei rays of the su. Do you khow ,hot our Ozore lol€t q4. dQ4tt\!ci.d? Il olreadY hod holes lhai dllow the ulrroviolet rdys to .4dt ihe @rrh. How do6 this hdpPei? Does th. in rc$e of poPuldioh h@€ sonething 'to do tr,lh ir? Yes, rhe I6i grov/irts PoPuldiion .odribuied o lot be@use 6 th' populotion incre3es, rhe u5e of refrigerd'tors, d€rosol lProvs 6nd pl4srics 6bo ihcre&s6. The sid producls coiiojn chemicol called Chlorofluorocdrbons (CFCS) which is mix wafh ihe dir in ihe ormosPher€. As o resulr. ihe hcrmfirl chernicol r€oches the Prolectiw ldver dnd lhrowh. hole in {hid ult@iolzi cahders aid cai4.ct3 ,F.*Y.iis hi!586$q€9.7,- Ho$ doas dcid rdin form? Is cid roii hdmful ro rEn? In the prcvious dis.ussions, yodt€ t.on€d rhd more vel .1e3 dnd fdctori€s or€ necded fo het the iii:.e.siry number o{ P@Pla. Lefs now fihd af hd f@tot.i€s dnd vehicle! .ontribure in the forrEtion of ocid When foctories 6nd whi.ler give off woste gd..3 ,hot will ,nix on lhe noisture i. rhe oir, it will ihen Produ.e sulPhu.i. ocld dnd Nitri. o.id. 'Ihe clol,Jd folb will ,h€h obsorb rhese ccids ond ehei ihe clold f.lls os .oin, ih. ccid is ahady Pdrr of itU/ha d.id ftin falls oh lok"!, ,46 or ocan ih€ fish sill die d.d if h fdlls oh fopnlonds,lhe pldni. together oith the soil B desrroyed. When you inhole dir with Niiric acid, your blood will los. irs @pobilily io fonspori Oxyg€h to your diff€.ai bodY Po.i3. ScieniisB include other rorns oJ dcidic pr€cipiigrion. Thes€ drc nisi, Do you krcw ihot Nuclerr power slotionr Use .adiodctive ,ndie.ials in producirE fuels, yet, rhey do and those .odioactiw rndlqlotE gi\e otf radio'ting en.rgy thoi is harmrul 'to livirq thilEs. wlren rodiotion enlert ihe body ot living things it {ill srq rhere for o lorg ,eriod of ri'ne. Exonple fhe rodiqtion vG srilled to the c.m. Then rhe @rn will be aie by rhe chicken, the .odiotion o the c.rn 'rill also 'tronsf€r to the chi.k€n. Wha on individuol als ihe nat of the chickeh sith mdiarion, helshe rill .ko oblorb ihe rodi@.tirc mtaid that will destrcy hB/her .€lls ond ruket hnn/hd si.r. Over-populoiion .on leld to food shoridg€, wdter shorroqe, housiB probl€ms, qdrbog€ probl€rs, lock of halrh sdi.e. tisa ol clit@ rote, oir ond woi€r pollution, uhanpl6ynat, eiergy 5horr69e, grenhoq3€ efreci, desrruction o( th. ozo@ lat/e?, rci.l roi. olld e.l€d. watta
CARBOHYDRATES Carbohydrates are organic compounds composed of carbon, hydrogen, and oxygen in a ratio of about one carbon atom to two hydrogen atoms to one oxygen atom. The number of carbon atoms in a carbohydrate varies. Some carbohydrates serve as a source of energy. Other carbohydrates are used as structural materials. Carbohydrates can exist as monosaccharides, disaccharides, or polysaccharides. Monosaccharides A monomer of a carbohydrate is called a monosaccharide (MAHN-oh-SAK-uh-RIED). A monosaccharide—or simple sugar— contains carbon, hydrogen, and oxygen in a ratio of 1:2:1. The gen- eral formula for a monosaccharide is written as (CH2O)n, where n is any whole number from 3 to 8. For example, a six-carbon mono- saccharide, (CH2O)6, would have the formula C6H12O6. The most common monosaccharides are glucose, fructose, and galactose, as shown in Figure 3-6. Glucose is a main source of energy for cells. Fructose is found in fruits and is the sweetest of the monosaccharides. Galactose is found in milk. Notice in Figure 3-6 that glucose, fructose, and galactose have the same molecular formula, C6H12O6, but differing structures. The different structures determine the slightly different properties of the three compounds. Compounds like these sugars, with a single chemical formula but different structural forms, are called isomers (IE-soh-muhrz). SECTION 2 OBJECTIVES ● Distinguish between monosaccharides, disaccharides, and polysaccharides. ● Explain the relationship between amino acids and protein structure. ● Describe the induced fit model of enzyme action. ● Compare the structure and function of each of the different types of lipids. ● Compare the nucleic acids DNA and RNA. VOCABULARY carbohydrate monosaccharide disaccharide polysaccharide protein amino acid peptide bond polypeptide enzyme substrate active site lipid fatty acid phospholipid wax steroid nucleic acid deoxyribonucleic acid (DNA) ribonucleic acid (RNA) nucleotide C HO H C H OH C OH H C CH2OH H C H OH O Glucose C OH C O H OH C OH H CH2OH C H CH2OH Fructose C H HO C OH H C OH H C CH2OH H C H OH O Galactose Glucose, fructose, and galactose have the same chemical formula, but their structural differences result in different properties among the three compounds. FIGURE 3-6 Copyright © by Holt, Rinehart and Winston. All rights reserved. 56 CHAPTER 3 Disaccharides and Polysaccharides In living things, two monosaccharides can combine in a condensa- tion reaction to form a double sugar, or disaccharide (die-SAK-e-RIED). For example in Figure 3-4, the monosaccharides fructose and glu- cose can combine to form the disaccharide sucrose. A polysaccharide is a complex molecule composed of three or more monosaccharides. Animals store glucose in the form of the polysaccharide glycogen. Glycogen consists of hundreds of glucose molecules strung together in a highly branched chain. Much of the glucose that comes from food is ultimately stored in your liver and muscles as glycogen and is ready to be used for quick energy. Plants store glucose molecules in the form of the polysaccha- ride starch. Starch molecules have two basic forms—highly branched chains that are similar to glycogen and long, coiled, unbranched chains. Plants also make a large polysaccharide called cellulose. Cellulose, which gives strength and rigidity to plant cells, makes up about 50 percent of wood. In a single cellu- lose molecule, thousands of glucose monomers are linked in long, straight chains. These chains tend to form hydrogen bonds with each other. The resulting structure is strong and can be broken down by hydrolysis only under certain conditions. PROTEINS Proteins are organic compounds composed mainly of carbon, hydrogen, oxygen, and nitrogen. Like most of the other biological macromolecules, proteins are formed from the linkage of monomers called amino acids. Hair and horns, as shown in Figure 3-7a, are made mostly of proteins, as are skin, muscles and many biological catalysts (enzymes). Amino Acids There are 20 different amino acids, and all share a basic structure. As Figure 3-7b shows, each amino acid contains a central carbon atom covalently bonded to four other atoms or functional groups. A single hydrogen atom, highlighted in blue in the illustration, bonds at one site. A carboxyl group, —COOH, highlighted in green, bonds at a second site. An amino group, —NH2, highlighted in yel- low, bonds at a third site. A side chain called the R group, high- lighted in red, bonds at the fourth site. The main difference among the different amino acids is in their R groups. The R group can be complex or it can be simple, such as the CH3 group shown in the amino acid alanine in Figure 3-7b. The differences among the amino acid R groups gives different proteins very different shapes. The different shapes allow pro- teins to carry out many different activities in living things. Amino acids are commonly shown in a simplified way such as balls, as shown in Figure 3-7c. (a) Many structures, such as hair and horns are made of proteins. (b) Proteins are made up of amino acids. Amino acids differ only in the type of R group (shown in red) they carry. Polar R groups can dissolve in water, but nonpolar R groups cannot. (c) Amino acids have complex structures, so, in this and other textbooks, they are often simplified into balls. FIGURE 3-7 (b) Alanine (an amino acid) (c) Simplified version of amino acid CH3 H N OH C C H O H (a) Copyright © by Holt, Rinehart and Winston. All rights reserved. BIOCHEMISTRY 57 H H N C C OH H O H CH3 H2O Glycine Alanine H N OH C C H O H H H N C C H O H CH3 N OH C C H O H (a) (b) (a) The peptide bond (shaded blue) that binds amino acids together to form a polypeptide results from a condensation reaction that produces water. (b) Poly- peptides are commonly shown as a string of balls in this textbook and elsewhere. Each ball represents an amino acid. FIGURE 3-8 Substrate Products Enzyme 1 2 3 In the induced fit model of enzyme action, the enzyme can attach only to a substrate (reactant) with a specific shape. The enzyme then changes and reduces the activation energy of the reaction so reactants can become products. The enzyme is unchanged and is available to be used again. 3 2 1 FIGURE 3-9 Dipeptides and Polypeptides Figure 3-8a shows how two amino acids bond to form a dipeptide (die-PEP-TIED). In this condensation reaction, the two amino acids form a covalent bond, called a peptide bond (shaded in blue in Figure 3-8a) and release a water molecule. Amino acids often form very long chains called polypeptides (PAHL-i-PEP-TIEDZ). Proteins are composed of one or more polypep- tides. Some proteins are very large molecules, containing hun- dreds of amino acids. Often, these long proteins are bent and folded upon themselves as a result of interactions—such as hydrogen bonding—between individual amino acids. Protein shape can also be influenced by conditions such as temperature and the type of solvent in which a protein is dissolved. For exam- ple, cooking an egg changes the shape of proteins in the egg white. The firm, opaque result is very different from the initial clear, runny material. Enzymes Enzymes—RNA or protein molecules that act as biological catalysts—are essential for the functioning of any cell. Many enzymes are proteins. Figure 3-9 shows an induced fit model of enzyme action. Enzyme reactions depend on a physical fit between the enzyme molecule and its specific substrate, the reactant being catalyzed. Notice that the enzyme has folds, or an active site, with a shape that allows the substrate to fit into the active site. An enzyme acts only on a specific substrate because only that substrate fits into its active site. The linkage of the enzyme and substrate causes a slight change in the enzyme’s shape. The change in the enzyme’s shape weakens some chemical bonds in the substrate, which is one way that enzymes reduce activation energy, the energy needed to start the reaction. After the reaction, the enzyme releases the products. Like any catalyst, the enzyme itself is unchanged, so it can be used many times. An enzyme may not work if its environment is changed. For example, change in temperature or pH can cause a change in the shape of the enzyme or the substrate. If such a change happens, the reaction that the enzyme would have catalyzed cannot occur.
Measuring the Effectiveness of police strategies and operations Clearance rates Def: The proportion of incidents known to the police that result in teh identification of a suspect Crime Displacement Def: relocation-due to the effective crime prevention, crime response initiates criminal activity from one local to another Professional Model of Policing Model of police work, reactive, incident driven and centred on random patrol Three Rs: random patrol, rapid response and reactive investigation Community policing Def: policing centred on police-community partnership and problem-solving The three ps: prevention, problem solving and partnership with the proactive role Community-based strategic policing Def: The model incorporates community policing with prevention, crime response and crime attack approaches Community engagement, police services strategic in their policies and operations Crime Analytics Sophisticated programs, and crime maps, provide intelligence to police officers in patrol and investigative units Intelligence-led policing: guided by collection, and analysis of information informs police decision-making Compstat: Increase effectiveness, and efficiency of police service while holding police personnel accountable for crime reduction Predictive policing: statistical analysis, identify time and location likely to occur Limited analytical capacity and not able to provide their officers with real-time information Biased policing certain areas, or persons, being identified as important for police attention in predictive policing How Predictive Policing Software Works The Police and the community Public Attitudes toward and Confidence in the police Community-based strategic policing: Recruitment, and deployment of volunteers in community police stations, storefronts Foot and bike patrols Team policing Restorative Justice Approaches Alternative for addressing, and resolving crime, needs of victims, offenders and the community Victim offender meditation Circle sentencing Community holistic healing programss Family group conferences Crime Prevention and Response Strategies Crime Prevention progemas Aimed at reducing crime, generating community involvement and heightening citizens; perceptions of safety Primary crime prevention programs opportunities for criminal offences and alter those conditions Secondary crime prevention programs focus on areas that produce crime and disorder Tertiary crime prevention programs are designed to prevent youth and adults from reoffending The Broken Windows Approach If minor crimes are left unaddressed in an environment, more serious crimes will emerge (originated in New York City in the 1980’s) “The exictsnce of unchecked and uncontrolled mirror incivilites in a neighbourhood- for example, panhandling, public drunkenness, vandalism and graffiti-produces an atmosphere conducive to more serious crime.” R.H. Burke Zero tolerance policing Zero tolerance policing: Strict order maintenance approach- specific area, coupled with high police visibility and presence Quality of life policing: Increased police visibility improves conditions in an area by targeting disruptive and annoying behaviour Problem Oritented policing (POP) Strategy, the idea that police should address teh cause of recurrent crime and disorder Root causes of recurring problems Solutions to problems Collabortaion with community SARA (scanning, analysis, response and assessment) problem-solving model helps officers identify, and respond to problems with the assistance of agencies, organizations, community groups The Police and Vulnerable/ At risk groups Persons with Mental Illness Patrol officers encountering more and more persons with mental illness (PwMi) Number of these end trragically Number of incidents increased significantly following deinstitutionalization of the mentally ill - in 1960 and 1970 De facto (in fact) mental health workers, first responders Crisis intervention training (CIT) Assertive outreach teams Assertive community treatment (ACT) teams Indigenouse, Vulnerable, and Marginalized women Sexual assault one of most underreported crimed. 1 in 20 incidents report to police. Many Women Do not want to deal with police Believe police would not take allegation seriously Language, cultural barriers Distrust the police Fear repercussions Missing and Murdered Indigenous women Canada, unknown number of missing and murdered indigenous women 2016, federal government announced National inquiry into Missing and Murdered Indigennouse women and girls Three goals of MMIWG 1. Finding the truth 2. Honouring the truth 3. Giving life to the truth as a path of healing
Understanding Quantum Theory of Electrons in Atoms The goal of this section is to understand the electron orbitals (location of electrons in atoms), their different energies, and other properties. The use of quantum theory provides the best understanding to these topics. This knowledge is a precursor to chemical bonding. As was described previously, electrons in atoms can exist only on discrete energy levels but not between them. It is said that the energy of an electron in an atom is quantized, that is, it can be equal only to certain specific values and can jump from one energy level to another but not transition smoothly or stay between these levels. The energy levels are labeled with an n value, where n = 1, 2, 3, …. Generally speaking, the energy of an electron in an atom is greater for greater values of n. This number, n, is referred to as the principal quantum number. The principal quantum number defines the location of the energy level. It is essentially the same concept as the n in the Bohr atom description. Another name for the principal quantum number is the shell number. The shells of an atom can be thought of concentric circles radiating out from the nucleus. The electrons that belong to a specific shell are most likely to be found within the corresponding circular area. The further we proceed from the nucleus, the higher the shell number, and so the higher the energy level (Figure 9.4.1). The positively charged protons in the nucleus stabilize the electronic orbitals by electrostatic attraction between the positive charges of the protons and the negative charges of the electrons. So the further away the electron is from the nucleus, the greater the energy it has. This quantum mechanical model for where electrons reside in an atom can be used to look at electronic transitions, the events when an electron moves from one energy level to another. If the transition is to a higher energy level, energy is absorbed, and the energy change has a positive value. To obtain the amount of energy necessary for the transition to a higher energy level, a photon is absorbed by the atom. A transition to a lower energy level involves a release of energy, and the energy change is negative. This process is accompanied by emission of a photon by the atom. The following equation summarizes these relationships and is based on the hydrogen atom: The values nf and ni are the final and initial energy states of the electron. The principal quantum number is one of three quantum numbers used to characterize an orbital. An atomic orbital, which is distinct from an orbit, is a general region in an atom within which an electron is most probable to reside. The quantum mechanical model specifies the probability of finding an electron in the three-dimensional space around the nucleus and is based on solutions of the Schrödinger equation. In addition, the principal quantum number defines the energy of an electron in a hydrogen or hydrogen-like atom or an ion (an atom or an ion with only one electron) and the general region in which discrete energy levels of electrons in a multi-electron atoms and ions are located. Another quantum number is l, the angular momentum quantum number. It is an integer that defines the shape of the orbital, and takes on the values, l = 0, 1, 2, …, n – 1. This means that an orbital with n = 1 can have only one value of l, l = 0, whereas n = 2 permits l = 0 and l = 1, and so on. The principal quantum number defines the general size and energy of the orbital. The l value specifies the shape of the orbital. Orbitals with the same value of l form a subshell. In addition, the greater the angular momentum quantum number, the greater is the angular momentum of an electron at this orbital. Orbitals with l = 0 are called s orbitals (or the s subshells). The value l = 1 corresponds to the p orbitals. For a given n, p orbitals constitute a p subshell (e.g., 3p if n = 3). The orbitals with l = 2 are called the d orbitals, followed by the f-, g-, and h-orbitals for l = 3, 4, 5, and there are higher values we will not consider. There are certain distances from the nucleus at which the probability density of finding an electron located at a particular orbital is zero. In other words, the value of the wavefunction ψ is zero at this distance for this orbital. Such a value of radius r is called a radial node. The number of radial nodes in an orbital is n – l – 1. Consider the examples in Figure 9.4.2. The orbitals depicted are of the s type, thus l = 0 for all of them. It can be seen from the graphs of the probability densities that there are 1 – 0 – 1 = 0 places where the density is zero (nodes) for 1s (n = 1), 2 – 0 – 1 = 1 node for 2s, and 3 – 0 – 1 = 2 nodes for the 3s orbitals. The s subshell electron density distribution is spherical and the p subshell has a dumbbell shape. The d and f orbitals are more complex. These shapes represent the three-dimensional regions within which the electron is likely to be found. Principal quantum number (n) & Orbital angular momentum (l): The Orbital Subshell: https://youtu.be/ms7WR149fAY If an electron has an angular momentum (l ≠ 0), then this vector can point in different directions. In addition, the z component of the angular momentum can have more than one value. This means that if a magnetic field is applied in the z direction, orbitals with different values of the z component of the angular momentum will have different energies resulting from interacting with the field. The magnetic quantum number, called ml, specifies the z component of the angular momentum for a particular orbital. For example, for an s orbital, l = 0, and the only value of ml is zero. For p orbitals, l = 1, and ml can be equal to –1, 0, or +1. Generally speaking, ml can be equal to –l, –(l – 1), …, –1, 0, +1, …, (l – 1), l. The total number of possible orbitals with the same value of l (a subshell) is 2l + 1. Thus, there is one s-orbital for ml = 0, there are three p-orbitals for ml = 1, five d-orbitals for ml = 2, seven f-orbitals for ml = 3, and so forth. The principal quantum number defines the general value of the electronic energy. The angular momentum quantum number determines the shape of the orbital. And the magnetic quantum number specifies orientation of the orbital in space, as can be seen in Figure 9.4.3. Figure 9.4.4 illustrates the energy levels for various orbitals. The number before the orbital name (such as 2s, 3p, and so forth) stands for the principal quantum number, n. The letter in the orbital name defines the subshell with a specific angular momentum quantum number l = 0 for s orbitals, 1 for p orbitals, 2 for d orbitals. Finally, there are more than one possible orbitals for l ≥ 1, each corresponding to a specific value of ml. In the case of a hydrogen atom or a one-electron ion (such as He+, Li2+, and so on), energies of all the orbitals with the same n are the same. This is called a degeneracy, and the energy levels for the same principal quantum number, n, are called degenerate energy levels. However, in atoms with more than one electron, this degeneracy is eliminated by the electron–electron interactions, and orbitals that belong to different subshells have different energies. Orbitals within the same subshell (for example ns, np, nd, nf, such as 2p, 3s) are still degenerate and have the same energy. While the three quantum numbers discussed in the previous paragraphs work well for describing electron orbitals, some experiments showed that they were not sufficient to explain all observed results. It was demonstrated in the 1920s that when hydrogen-line spectra are examined at extremely high resolution, some lines are actually not single peaks but, rather, pairs of closely spaced lines. This is the so-called fine structure of the spectrum, and it implies that there are additional small differences in energies of electrons even when they are located in the same orbital. These observations led Samuel Goudsmit and George Uhlenbeck to propose that electrons have a fourth quantum number. They called this the spin quantum number, or ms. The other three quantum numbers, n, l, and ml, are properties of specific atomic orbitals that also define in what part of the space an electron is most likely to be located. Orbitals are a result of solving the Schrödinger equation for electrons in atoms. The electron spin is a different kind of property. It is a completely quantum phenomenon with no analogues in the classical realm. In addition, it cannot be derived from solving the Schrödinger equation and is not related to the normal spatial coordinates (such as the Cartesian x, y, and z). Electron spin describes an intrinsic electron “rotation” or “spinning.” Each electron acts as a tiny magnet or a tiny rotating object with an angular momentum, even though this rotation cannot be observed in terms of the spatial coordinates. The magnitude of the overall electron spin can only have one value, and an electron can only “spin” in one of two quantized states. One is termed the α state, with the z component of the spin being in the positive direction of the z axis. This corresponds to the spin quantum number ms=12. The other is called the β state, with the z component of the spin being negative and ms=−12. Any electron, regardless of the atomic orbital it is located in, can only have one of those two values of the spin quantum number. The energies of electrons having ms=−12 and ms=12 are different if an external magnetic field is applied. Figure 9.4.5 illustrates this phenomenon. An electron acts like a tiny magnet. Its moment is directed up (in the positive direction of the z axis) for the 12 spin quantum number and down (in the negative z direction) for the spin quantum number of −12. A magnet has a lower energy if its magnetic moment is aligned with the external magnetic field (the left electron) and a higher energy for the magnetic moment being opposite to the applied field. This is why an electron with ms=12 has a slightly lower energy in an external field in the positive z direction, and an electron with ms=−12 has a slightly higher energy in the same field. This is true even for an electron occupying the same orbital in an atom. A spectral line corresponding to a transition for electrons from the same orbital but with different spin quantum numbers has two possible values of energy; thus, the line in the spectrum will show a fine structure splitting. The Pauli Exclusion Principle An electron in an atom is completely described by four quantum numbers: n, l, ml, and ms. The first three quantum numbers define the orbital and the fourth quantum number describes the intrinsic electron property called spin. An Austrian physicist Wolfgang Pauli formulated a general principle that gives the last piece of information that we need to understand the general behavior of electrons in atoms. The Pauli exclusion principle can be formulated as follows: No two electrons in the same atom can have exactly the same set of all the four quantum numbers. What this means is that electrons can share the same orbital (the same set of the quantum numbers n, l, and ml), but only if their spin quantum numbers ms have different values. Since the spin quantum number can only have two values (±12), no more than two electrons can occupy the same orbital (and if two electrons are located in the same orbital, they must have opposite spins). Therefore, any atomic orbital can be populated by only zero, one, or two electrons. The properties and meaning of the quantum numbers of electrons in atoms are briefly
Received: 26 November 2019 Revised: 10 January 2020 Accepted: 19 January 2020 DOI: 10.1111/obr.13005 PEDIATRICS/PHYSIOLOGY Adipokines: A gear shift in puberty Desirée Nieuwenhuis | Natàlia Pujol-Gualdo Amanda J. Kiliaan Department of Anatomy, Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Preclinical Imaging Center PRIME, Nijmegen, The Netherlands Correspondence Amanda J. Kiliaan, PhD, Associate Professor, Department of Anatomy, Donders Institute for Brain, Cognition, and Behaviour, Preclinical Imaging Center PRIME, Radboud university medical center, 6500 HB Nijmegen, Geert Grooteplein 21N 6525 EZ Nijmegen, The Netherlands. Email: amanda.kiliaan@radboudumc.nl Funding information Europees Fonds voor Regionale Ontwikkeling (EFRO), Grant/Award Number: BriteN 2016 1 | INTRODUCTION The prevalence of obesity in adolescents and children is increasing in | Ilse A.C. Arnoldussen | Summary In this review, we discuss the role of adipokines in the onset of puberty in children with obesity during adrenarche and gonadarche and provide a clear and detailed overview of the biological processes of two major players, leptin and adiponectin. Adipokines, especially leptin and adiponectin, seem to induce an early onset of puberty in girls and boys with obesity by affecting the hypothalamic-pituitary- gonadal (HPG) axis. Moreover, adipokines and their receptors are expressed in the gonads, suggesting a role in sexual maturation and reproduction. All in all, adipokines may be a clue in understanding mechanisms underlying the onset of puberty in child- hood obesity and puberty onset variability. KEYWORDS adipokines, obesity, puberty 1,2 the age of 5 years were overweight or were with obesity in 2016, and 3 Obesity is defined by an excessive accumulation of white adipose tissue (WAT), and it is often indicated by a body mass index (BMI) 4 above 30. Two main types of adipose tissue were described: WAT and brown adipose tissue (BAT), which differ in morphology and func- 5-7 Ilse A.C. Arnoldussen and Amanda J. Kiliaan contributed equally to this work. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2020 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation Obesity Reviews. 2020;21:e13005. wileyonlinelibrary.com/journal/obr 1 of 10 https://doi.org/10.1111/obr.13005 alarming rates. Specifically, worldwide, 41 million children below this number is expected to increase to 70 million in 2025. obesity is associated with various severe health complications, includ- ing increased risk of diabetes mellitus type 2, hypertension, heart dis- eases, and disturbances in sex hormone levels. 5,6 and mitochondria and plays a role in thermogenesis. Adipocytes in tion. BAT consists of adipocytes containing multiple lipid droplets WAT contain only a few mitochondria and a single lipid droplet. Adipose tissue has several functions including the storage of energy, thermogenesis, and the production and secretion of adipokines Generally, two physiological processes, adrenarche and gonadarche, 11,24 Childhood 5,7,8 a key role in puberty onset. Puberty is known as a period through which the body changes physically, being a physiological process resulting in the maturation of children, i.e. they develop sexual characteristics and obtain reproduc- 9,11 Adipokines are involved in a number of physiological processes including blood pressure, metabo- lism, glucose, and vascular homeostasis and may play amongst others 8-10 (hormones, cytokines, and peptides). tive functions. between obesity and puberty,2,12-23 the biological mechanisms under- lying obesity and puberty onset remain unclear. Hereafter, we review in detail the role of adipokines in the onset of puberty in childhood obesity. Although many studies have shown associations 2 | INITIATION OF PUBERTY PHYSIOLOGICAL PROCESSES IN THE interact to regulate the onset of puberty. During adrenarche, the adrenal cortex secretes steroid hormones (including 2 of 10 NIEUWENHUIS ET AL. androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate (DHEAS), androstenedione, and cortisol), insulin-like growth factor, and growth hormone, which contribute to the pubertal insights on new genetic loci (e.g. melanocortin-4 receptor, mitochon- drial carrier 2, and mitogen-activated protein kinase 13) and on sev- eral pathways that regulate the timing of puberty; however, it partly 34 9,24,25 Both adrenarche and gonadarche are involved in the development growth spurt, body odor, skin oiliness, and skeletal maturation. explains puberty timing variation. Thereby, defining the role of 25 adipokines is of importance in elucidating the variability in puberty as the expression of adipokines is sex-specific and is altered with body composition, adiposity, and during growth spurts. Moreover, adipokines and their receptors are expressed in gonads and several brain regions suggesting involvement in the onset of puberty and sex- ual maturation. Lastly, adipokines interfere in processes regulating timing and duration of puberty, for instance in the HPA and HPG axes which are both key players during adrenarche and gonadarche. Involvement of adipokines in the onset of puberty and specifically in individuals with obesity will be further reviewed in the next 2,24 3 | Puberty onset in girls is assessed using different markers, such as thelarche (breast development), menarche (the start of of pubic hair. pituitary-gonadal (HPG) axis is activated,2,26 and several hormones have been identified to participate in the activation of the HPG axis During gonadarche (Figure 1), the hypothalamic- 2,27 Kisspeptin, neurokinin B, and dynorphin are released by specialized including kisspeptin, neurokinin B, dynorphin, leptin, and ghrelin. 28 key regulator of the pulsatile secretion of gonadotropin releasing neurons, the KNDy neurons in the hypothalamus. Kisspeptin is a 29,30 B stimulates, and dynorphin inhibits the release of kisspeptin, which hormone (GnRH) from the hypothalamus. In addition, neurokinin implies that both coordinate a pulsatile release of kisspeptin. 31 Sub- sections. sequently, the activated HPG axis induces the pituitary gland to secrete luteinising hormone (LH) and follicle stimulating hormone (FSH). As a result, gametogenesis occurs, and the gonads will release sex hormones. Consequently, secondary sex characteristics develop including breast development in girls and an increased testicular vol- 2,26,32 is possibly due to differences in levels of body fat, hypothalamic-pitui- THE ONSET OF PUBERTY IN GIRLS ume in boys. The age at puberty onset varies greatly among individuals, which 19 35 menstruation), and pubic hair development. 33 genome-wide association studies have provided important new tary-adrenal (HPA) axis activity, and genetic background. Recent The average age of However, this age differs between cultures and ethnicities, and since 1980, age at menarche is girls at start of menarche is 12.4 years. 36 significantly decreasing. 36-39 F I G U R E 1 Hormonal regulation in the initiation of puberty in boys and girls. The secretion of kisspeptin, neurokinin B, and dynorphin from KNDy neurons initiate the release of gonadotropin releasing hormone (GnRH) from the hypothalamus. This activates the pituitary gland to produce and secrete luteinising hormone (LH) and follicle stimulating hormone (FSH), which in turn stimulate the gonads to produce estrogen and testosterone in girls and boys, respectively 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License NIEUWENHUIS ET AL. 3 of 10 T A B L E 1 Summary of included studies Authors Year Country Study Design Primary Outcome Sex Sample Size (n) Age (y) Data Collection Lian et al21 2019 China Cross-sectional Puberty starts earlier in Chinese Han girls with obesity compared with Chinese Han girls with normal weight. Girls 2996 9-19 2012 and 2013 Biro et al12 Lazzeri et al20 2018 USA 2018 Italy Longitudinal Cross-sectional Body mass index had a greater effect on age at menarche than did race and ethnicity. Girls 946 6-16 2004-2014 Li et al23 2018 China Longitudinal For both, boys and girls, a higher BMI (ie, overweight and obese) is associated with earlier onset of puberty Girls Girls Boys Girls 542 Deng et al22 Flom et al15 2017 China Cross-sectional Increased BMI is associated with early timing spermarche and menarche. Boys Girls Girls 1278258 9-15 2005-2012 He et al24 Holmgren et al17 2017 China 2017 Sweden Cross-sectional Longitudinal Onset of puberty is not related to obesity in boys. Boys Boys Girls Girls 782 7-17 972 929 5839 Kelly et al19 2017 UK 2016 Brazil 2016 USA Longitudinal prospective cohort Higher BMI in girls is associated with the onset of menstruation at an earlier age. 11 10-18 11-17 Barcellos Gemelli et al25 Cross-sectional Longitudinal Excess weight is associated with early age of menarche. Girls 727 2014 2003-2009 Glass et al16 Lee et al26 In girls, but not in boys, greater adiposity is associated with the earlier onset of puberty. Boys Girls 135 Cabrera et al27 Leonibus et al14 2014 USA 2013 Italy Cross-sectional Longitudinal Thelarche occurred earlier than recently reported, while age of menarche remained unchanged. Girls 610 3-17.9 2007 2005-2012 Currie et al13 2012 Europe, USA, Canada Cross-sectional Overweight/obesity during childhood predicts the early onset of puberty in girls. Girls 20410 11, 13, 15 2005-2006 2017 USA Prospective birth cohort Overweight/obese status at the age of 7 ye was associated with increased risk of early menarche 788 From birth to menarche occurred Pregnancies 1959-1966 2016 USA Cross-sectional Boys with overweight enter puberty earlier compared with boys with normal weight or obesity, while puberty starts later in boys with obesity compared with boys with normal weight and overweight. Boys 3872 6-16 2005-2010 Overweight during childhood shows a relation with the early onset of puberty in girls. 6535 4259 695 11 15 5.8-12.2 2009/2010 2013/2014 2014-2017 Higher BMI during childhood is associated with early puberty. 2008 and 2009 2000-2002 Obesity during childhood is related to the earlier onset of puberty. Boys Girls 84 123 71 (Continues) 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 4 of 10 NIEUWENHUIS ET AL. 3.1 | Fat storage For the initiation of puberty, the timing of stimulation and/or inhibi- tion of different hormones is important, and additionally, a certain amount and distribution of body fat is needed in order to start menar- che, which emphasizes the importance of body fat. From an evolution- ary point of view, body fat increases in mammalian females during puberty onset, and it highlights the need to guarantee a healthy preg- 40 women with anorexia nervosa. particularly body fat localized predominantly on the gluteofemoral fat depots, is profoundly associated with start of menarche, more than nancy, offspring, and maternal survival. fat, sex-hormones, and neuroendocrine alterations can evolve in men- strual dysfunction, for instance, in women with severe obesity or in 41-43 44-46 to gluteofemoral fat depots suggesting that leptin may convey infor- amount of total body fat. mation on body fat distribution to the hypothalamus during puberty. An improper level of body Importantly, body fat distribution, Blood leptin levels are strongly related 45 3.2 | HPG axis The HPG axis is activated by the release of kisspeptin resulting in the release of GnRH from the hypothalamus, and LH and FSH from the pituitary gland. In girls, FSH is involved in the development of the folli- cles in the ovaries, and it promotes the secretion of estrogen. LH stim- ulates the production of androgen hormones and induces ovulation 48 9,47 the release of kisspeptin and neurokinin B, and kisspeptin thereby (Figure 1). The secretion of estrogen has an inhibitory effect on inhibits the GnRH release from the hypothalamus. pattern of GnRH is important for the regulation of the menstrual cycle. This roughly 28-day-cycle comprises several phases, including the follicular phase and luteal phase. During the follicular phase, increasing levels of FSH stimulate the maturation of follicles and the production of estrogen from the ovaries. This in turn inhibits the release of FSH from the pituitary gland. A high level of estrogen will induce the production of LH by the pituitary gland, resulting in ovula- tion. The matured follicle secretes progesterone thereby inhibiting the release of GnRH. When the corpus luteum is demolished, there is less 48 3.3 | Adipokines According to results from studies reported in Table 1, girls with obe- sity enter puberty earlier compared with girls with normal higher leptin concentrations inhibit the intake of food and increases inhibition of GnRH. As a consequence, the cycle will start again. whole process, starting from the activated HPG axis, results in the development of the secondary sex characteristics in girls including 9,47 thelarche and menarche. 13,14,16-23,49-51 weight. these girls might be found in the secretion of adipokines. For instance, leptin is positively associated with the amount of body fat. Generally, energy expenditure. 9,52-54 An explanation for the early onset of puberty in The expression This TABLE 1 (Continued) Authors Year Country Study Design Primary Outcome Sample Sex Size (n) Age (y) Data Collection Herman-Giddens et al28 2012 USA Cross-sectional Observed mean ages of beginning genital and pubic hair growth and early testicular volumes were earlier than in past studies, depending on the characteristic and race/ethnicity. Boys 4131 6-16 2005-2010 Sorensen et al29 Aksglaede et al30 2010 2009 Denmark Denmark Cross-sectional/longitudinal Longitudinal Puberty onset at earlier ages was associated with an increased BMI in boys. Boys 1528 5.8-19.9 1991-1993/2006-2008 1930-1969 Juul et al31 Ribeiro et al32 2007 2006 Denmark Portugal Retrospective cohort Cross-sectional Higher BMI is associated with early voice break. 11-15 10-15 1990-1999 Kaplowitz et al18 Abbreviation: BMI, body mass USA Cross-sectional The early onset of puberty in Caucasian girls is likely related to an increased BMI. 5-12 1992-1993 2001 index. The higher BMI in boys and girls at 7 y of age, the earlier they enter puberty. Boys 21 612 Girls 135 223 Boys 463 Boys 382 Girls 437 Girls 10 750 Early sexual maturation in boys and girls is associated with overweight. 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License NIEUWENHUIS ET AL. 5 of 10 Leptin may possibly play a role in adrenarche as its plasma level increases with higher levels of body fat and as it can modulate both girls. 33 ing adrenarche. In coherence, in children with obesity, the androgen These findings suggested that lower reproductive status was associated with higher total adiponectin concentrations and that a higher reproductive status was related to higher HMW adiponectin the HPA and HPG axes. These axes are functionally integrated dur- DHEAS was positively associated with leptin levels. Nevertheless, concentrations in girls. In addition, individuals with obesity often another study showed that enhanced adrenal androgen secretion in girls with premature adrenarche was not explained by leptin or BMI 55 ated with androgen levels in girls ; however, it was not related to levels. and IL-6. TNF-α alters, and IL-6 inhibits the expression of 56 8 In addition, the adipokine adiponectin was negatively associ- 57 differences of adiponectin seem to develop during the progression of 56 adiponectin (Figure 2). Thereby, a low level of total adiponectin and/or high levels of inflammatory cytokines in individuals with obe- sity can promote the onset of puberty. Many more adipokines are secreted by WAT including omentin, 52,65-67 9,36,62,68 adrenarche in girls with Prader-Willi syndrome. Interestingly, sex puberty. adrenarche; however, both are not required factors. Thus, leptin and adiponectin might be able to influence In gonadarche, leptin can stimulate the secretion of kisspeptin, and subsequently activation of the HPG axis, which eventually increases the expression of estrogen and androstenedione in the ova- 58 2,60 65-67 The expression of these ries (Figure 2). Ob gene in WAT, resulting in the synthesis and secretion of leptin. Thus, high levels of leptin promote onset of puberty in girls via secre- tion of kisspeptin, and estrogen stimulates leptin secretion addition- ally. Moreover, adiponectin can affect the HPG axis due to the expression of adiponectin receptors in the hypothalamus, pituitary In return, estrogen stimulates the expression of the 59 gland, and gonads. onset as it inhibits the secretion of kisspeptin and GnRH in the hypo- thalamus and the release of GH and LH in the pituitary gland, and 2,60-62 52,60 63 girls with central precocious puberty (CPP). Moreover, total adiponectin had negative correlations with progression of puberty in girls (defined by Tanner stages), whereas HMW adiponectin had FIGURE 2 Adipokinesaffectingthe initiation of puberty in girls. Leptin stimulates the release of kisspeptin in KNDy neurons, which activates the hypothalamus to produce gonadotropin releasing hormone (GnRH). In response to the release of GnRH, the pituitary gland secretes follicle stimulating hormone (FSH) and luteinising hormone (LH), which stimulates the ovaries to release estrogen resulting in the formation of secondary sex characteristics in girls. Estrogen stimulates the production of leptin. Adiponectin inhibits GnRH release resulting in reduced levels of GnRH and thereby a delayed onset of puberty. TNF- α and IL-6 inhibit the production of adiponectin and therefore stimulate the onset of puberty In detail, adiponectin is a regulator of puberty thereby inhibiting the onset of puberty (Figure 2). with obesity often have low levels of adiponectin. et al. showed that total adiponectin was significantly lower, whereas high molecular weight (HMW) adiponectin was significantly higher in ment. 55 63 develop a chronic low-grade inflammatory state, which can be indi- cated by a high level of circulating inflammatory cytokines like TNF-α 64 Individuals Sitticharoon positive associations with LH levels and the progression of puberty in 63 visfatin, resistin, and chemerin. and visfatin are expressed in the ovaries. adipokines in the ovaries suggests a role within the reproductive sys- tem; however, the exact biological processes have to be examined. Thus, specifically leptin, adiponectin, and inflammatory cytokines pro- duced by WAT could be permissive key players during an early onset of puberty in girls with obesity. As an exception, HMW adiponectin seems to have a stimulatory effect on peripheral repro- ductive function as HMW is not able to cross the blood brain 63 barrier. 4 | Markers that are used to assess puberty onset in boys are THE ONSET OF PUBERTY IN BOYS spermarche, voice break, testicular volume, and pubic hair develop- 35 spermarche develop in the early stages of puberty onset, voice In women, omentin, chemerin, While pubic hair development, larger testicular volume, and 69 testicular volume increases, which occurs at an average age of break usually appears in later stages of puberty. Generally, first 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 6 of 10 NIEUWENHUIS ET AL. 11.9 years, followed by the development of pubic hair at 12.2 years of average, and lastly, boys experience spermarche around an aver- 55 related with leptin levels. Thereby, leptin plausibly has a minor impact in adrenarche in boys. Since leptin receptors are found in the hypothalamus, pituitary gland, and testes, they might be involved in the onset of puberty by affecting the HPG axis during gonadarche. Leptin stimulates the release of kisspeptin and GnRH, and as a consequence, it accelerates the onset of puberty (Table 1, Figure 3). In contrast, adiponectin inhibits the secretion of GnRH, GH, LH, and FSH therewith delaying the onset of puberty. However, adiponectin levels are generally lower in men compared with women and even lower in men with obe- age age of 13.4 years. 70 4.1 | Fat storage Many aspects of the reproductive physiology are energetically demanding,71 and therefore, an adequate energy level is necessary. In boys, a dynamic change in body composition occurs around the age of 10 to 13 years, in which they gain approximately 40% of sity. culating inflammatory cytokines. levels can stimulate the HPG axis and therewith an early onset of puberty in boys. Nevertheless, leptin can inhibit the production of tes- 72 mostly consisting of lean mass, which causes exhaustion of most of fat. Subsequently, a growth spurt follows in which they gain tissue 72 in boys, an adequate amount of body fat is important in the onset of their body fat. These alterations in amount of body fat indicate that 4.2 | Puberty in boys is initiated by the release of kisspeptin. As mentioned before, this activates the HPG axis, resulting in the release of GnRH from the hypothalamus, and consequently the release of LH and FSH 9,74 puberty. tosterone from the testes, to estrogen (Figure 3). of the development of secondary sex characteristics in boys. Additionally, leptin can affect fertility in men as it can modulate the nutritional support of spermatogenesis, and moreover, dysfunction of spermatogenesis is associated with an increased leptin level and 73 58 2,60-62 HPG axis from the pituitary gland (Figure 1). and LH stimulates the secretion of testosterone from the testes, which inhibits the release of kisspeptin from the KNDy neurons and 9,48 in men, the release of kisspeptin is more consistent, causing a con- 29,48 subsequently GnRH from the hypothalamus. receptors expressed on KNDy neurons. In humans, KNDy neurons Contrarily to women, LH-induced testosterone levels lead to the stant release of LH. development of secondary sex characteristics in boys. differences between sexes in kisspeptin release are related to a sex- specific and sex steroid-dependent kisspeptin system as estrogen and progesterone modulate kisspeptin activity through the sex-steroid 48 in the infundibular nucleus are involved in negative and positive sex- 48 tal exposure to sex steroids and result in sex-specific differences in steroid feedbacks. kisspeptin release. These sexual dimorphisms are induced by perina- 75,76 4.3 | Adipokines The association between obesity and puberty onset in boys is rather controversial compared with findings in girls. Most studies reported an early onset of puberty in boys associated with increased ate adipose tissue from actual breast tissue. stages are more difficult to assess than female stages as boys lack a more determined marker such as menarche. Thirdly, puberty onset can be indicated by the activation of the HPG axis, and the presence of these secondary sex characteristics is the result of hormonal 2 14,17,22,23,50,51,77,78 BMI, 20,49 all while others reported no associations at Current markers used 79 16,80 or a delayed onset of puberty (Table 1). The presence of excessive adipose tissue can be involved in puberty onset in boys as the secretion of adipokines can modulate both adrenarche and gonadarche. Leptin can affect adrenarche by modulating both the HPG and HPA axes,33 and moreover, androgen levels were positively 55 nal androgen secretion in boys with premature adrenarche was not associated with plasma leptin levels. Nevertheless, enhanced adre- 9 In more detail, 61,62 adiponectin, and individuals with obesity often have high levels of cir- Moreover, inflammatory cytokines, TNF-α, and IL-6, inhibit expression of the leptin receptor in the testis. FSH induces spermatogenesis, too. function and role still have to be examined. 64 High leptin and low adiponectin and fat tissue can convert testosterone Both processes might result in the delay 29,61,79 81,82 In men, other adipokines like chemerin are found in the gonads 65 Thus, particularly high leptin and low adiponectin levels stimulate the HPG axis and thereby accelerate the onset of puberty in boys. Additionally, leptin can dysregulate the development of secondary sex characteristics and spermatogenesis by affecting testosterone levels and nutritional sup- port of spermatogenesis. 5 | LIMITATIONS AND FUTURE RESEARCH DIRECTIONS Even though multiple epidemiological studies have shown the link between puberty onset and obesity, there are some important limita- tions. Firstly, determining both the onset and stage of puberty is rather difficult. For instance, assessing the stage of breast develop- ment in girls with obesity is complicated as clinicians should differenti- 2 changes in response to the activated HPG axis. to determine the onset of puberty refer to secondary sex characteris- tics, such as testicular volume in boys and breast development in girls. A more accurate measurement of puberty onset would be to combine secondary sex characteristics with plasma or serum hormone level measurements such as LH, FSH, adipokines, e.g. leptin. Thereby, differences in puberty measurements could explain variations in the age of puberty onset between boys and girls within different Thereby, resistin is expressed in the testes of rats, but its exact 83 Secondly, male pubertal 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License NIEUWENHUIS ET AL. 7 of 10 FIGURE 3 Adipokines affecting the initiation of puberty in boys. Leptin activates kisspeptin secretion in KNDy neurons, this activates the production of gonadotropin releasing hormone (GnRH) from the hypothalamus. GnRH stimulates the pituitary gland to secrete follicle stimulating hormone (FSH) and luteinising hormone (LH), activating the production of testosterone from the testes allowing the development of secondary sex characteristics. Leptin also inhibits the production of testosterone, which may cause a delayed onset of puberty. Adiponectin inhibits GnRH release. Low levels of adiponectin, as a result of TNF-α and IL-6 expression, lead to a reduced inhibition of GnRH. In response to GnRH release, the pituitary gland will secrete FSH and LH, and the testes will produce testosterone resulting in the development of secondary sex characteristics in boys countries, and In addition, the inclusion of a of puberty. ferent time points is complicated, as subjects examined several decades ago presented pronounced differences concerning lifestyle patterns such as nutrition and exercise habits. Lastly, obesity or over- weight is often determined by BMI, a classification based on weight and height measurements. Additionally, it is important that all studies studies or across continents, ethnicities proper age range (8-16 years) is important when assessing the onset (Figure 4). 12-15,17,20-23,49,77-79,84,85 30,47 Furthermore, comparison between studies from dif- 86 Specifically in children, BMI is often dependent on age and growth use the same anthropometric standards and sex-specific cut-offs. 13,14,16-23,49-51,77-80 fat and would represent a more accurate measurement in its regard. Based on this review, several suggestions can be made for further research. Firstly, the roles of adipokines like resistin, chemerin, visfatin, and omentin in puberty onset, fertility, and sexual maturation should be examined in detail. Secondly, future research examining the onset of puberty should combine indicators of puberty onset (e.g. breast development or testicular volume) with plasma or serum hor- mone measurements such as LH, FSH, sex-steroids, adipokines (e.g. spurts. ment in case of growth spurts. distribution of body fat should be taken into account in determining puberty and obesity in children. For instance, the body adiposity index (BAI), which was introduced in 2011 by Bergman et al.,87 uses hip cir- cumference and height in order to estimate the percentage of body 87 Thereby, BMI is a less accurate measure- F I G U R E 4 87,88 Therefore, both percentage and Average age of puberty onset in Europe, China, and the United States according to several studies from Table 1. Age of puberty onset ranges from 8.47 to 13.33 years in girls and from 8.63 leptin), and body fat distribution (e.g. BAI,87 waist-hip ratio's and/or dual-energy X-ray absorptiometry (DXA)2). Additionally, defining con- sistent and general measurements of puberty in both boys and girls, combined with a proper age range (8-16 years), would facilitate the comparisons between different studies and their results. 12-15, 17, 20-23, 25-29, 31 to 13.7 years in boys. included if average age of markers used to assess puberty was not reported. Pink: girls. Blue: boys Studies (Table 1) were not 39, 56 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 8 of 10 NIEUWENHUIS ET AL. 6 | CONCLUSION In conclusion, epidemiological data regarding obesity and puberty onset in girls show similar outcomes as adiposity results in the early onset of puberty in girls. The majority of the studies examining boys with obesity indicate an early onset of puberty, while not all reported an earlier onset of puberty. In detail, high leptin, TNF-α, and IL-6 levels combined with low adiponectin levels stimulate the activation of the HPG axis in girls and boys with obesity, and 5, 45, 50, 51 REFERENCES 1. Kumar S, Kelly AS. Review of childhood obesity: from epidemiology, etiology, and comorbidities to clinical assessment and treatment. May- o Clin Proc. 2017;92(2):251-265. 2. Reinehr T, Roth CL. Is there a causal relationship between obesity and puberty? The Lancet Child & adolescent health. 2019;3(1):44-54. 3. WorldHealthOrganization. Facts and figures on childhood obesity. 2017. 4. Guglielmi V, Sbraccia P. Obesity phenotypes: depot-differences in adipose tissue and their clinical implications. Eat Weight Disord. 2018; 23(1):3-14. 5. Gomez-Hernandez A, Beneit N, Diaz-Castroverde S. Escribano O. 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BMC Womens Health. 2018;18(1):168-174. thereby an early onset of obesity. leptin can inhibit the production of testosterone in boys and subse- quently inhibit the development of secondary sex characteristics affecting spermatogenesis. for other adipokines, like resistin and omentin, are present in the testes and ovaries suggesting a role in puberty or reproduction; 58, 71 however, their plausible function is still unknown. that adipokines may be key regulators in an early onset of puberty in both girls and boys with obesity, specifically by affecting the HPG axis during gonadarche. Future research should focus on assessing puberty onset by measuring consistent puberty markers and determine the percentage of body fat and its distribution and adipokines and hormone serum levels particularly involved in the HPG axis. CONFLICTS OF INTEREST The authors declare no conflict of interest. FUNDING INFORMATION This research was funded by Europees Fonds voor Regionale Ontwikkeling (EFRO), project BriteN 2016. ORCID Ilse A.C. Arnoldussen Amanda J. Kiliaan https://orcid.org/0000-0002-7395-5284 https://orcid.org/0000-0002-2158-6210 13, 14, 16-26, 29-32 Furthermore, several receptors Nevertheless, We conclude Search strategy We searched PubMed for articles published before Novem- ber 15th, 2019 using relevant keywords, including ‘onset of puberty and adiposity/obesity’, ‘onset of puberty’, ‘children with obesity’, ‘adipose tissue’, ‘childhood obesity’, ‘adiposity’, ‘obesity’, ‘adipokine(s)’, ‘HPG axis’, ‘adipokines ovary/ova- ries’, or ‘adipokines testes’, either alone or in combination. 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Generate 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) 29
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