DOI: https://doi.org/10.22141/2224-0551.15.4.2020.208476

Phenotypes of obesity in children, clinical manifestations and genetic associations

A.E. Abaturov, A.A. Nikulinа

Abstract


The literature review presents modern ideas about molecular genetic features, clinical manifestations of phenotypes of obesity in children. The development of obesity results from the imbalance between energy intake and expenditure over a long period. Currently, among phenogenic obesity cases, two phenotypes are distinguished: one of which is characterized by the absence of metabolic disorders, called metabolically healthy obese (MHO), and the second, due to the presence of metabo­lic complications of obesity, is metabolically unhealthy obesity (metabolically unhealthy obese — MUO). The main genomic representatives that participate in the regulation of energy consumption are the genes ghrelin, leptin, leptin receptors, the gene associated with mass and obesity, the melanocortin 4 receptor gene, the glucagon-like peptide 1, and cholecystokinin. In contrast to the MHO phenotype, which is mainly due to changes in the activity of genes expressed in the brain; the MUO phenotype is associated with genes, most of which are mainly expressed in peripheral tissues. Genetic features of the expression of peri­pheral tissues involved in adipogenesis determine the distribution of excess adipose tissue: a predominant increase in the mass of subcutaneous adipose tissue leads to the development of the MHO phenotype, and excess weight of visceral and ectopic adipose tissue leads to the appearance of the MUO phenotype. Excess weight of subcutaneous fat does not lead to systemic me­tabolic disorders, but it is a transitional phenomenon in MHO, while visceral obesity and the accumulation of ectopic fat in the liver, pancreas, heart tissues and skeletal muscles are causally associated with low-grade inflammation, insulin resistance, impaired glucose metabolism and the development of cardiovascular disease and is typical for the MUO phenotype. The absence of generally accepted criteria for verifying the phenotype of obesity requires the search for new markers for identifying disorders of various metabolic pathways that would allow us to reliably distinguish MHO and MUO.

Keywords


obesity; phenotypes; genetic associations; children; review

References


Abaturov AE. Metabolic syndrome in children (lecture). Tavricheskiy Mediko-Biologicheskiy Vestnik. 2007;10:57-65. (in Russian).

Abaturov AE. Features of the metabolic syndrome in children. Dytiachyi likar. 2011;(11):54-61. (in Russian).

Bocharova OV, Teplyakova ED. Children and adolescents’ obesity is the 21st century health problem. Kazan Medical Journal. 2020;101(3):381-388. doi:10.17816/KMJ2020-381. (in Russian).

Vasyukova OV. Obesity in Children and Adolescents: Diagnosis Criteria. Obesity and Metabolism. 2019;16(1):70-73. doi:10.14341/omet10170. (in Russian).

Evdokimova EY, Popova UY. Obesity in children. Metabolic syndrome markers. Vestnik Soveta molodyh učënyh i specialistov Čelâbinskoj oblasti. 2017;1(17);16-19. (in Russian).

Alalwan TA. Phenotypes of Sarcopenic Obesity: Exploring the Effects on Peri-Muscular Fat, the Obesity Paradox, Hormone-Related Responses and the Clinical Implications. Geriatrics (Basel). 2020;5(1):8. doi:10.3390/geriatrics5010008.

Apalasamy YD, Ming MF, Rampal S, Bulgiba A, Mohamed Z. Association of melanocortin-4 receptor gene polymorphisms with obesity-related parameters in Malaysian Malays. Ann Hum Biol. 2013;40(1):102-106. doi:10.3109/03014460.2012.720709.

Bains V, Kaur H, Badaruddoza B. Association analysis of polymorphisms in LEP (rs7799039 and rs2167270) and LEPR (rs1137101) gene towards the development of type 2 diabetes in North Indian Punjabi population. Gene. 2020;754:144846. doi:10.1016/j.gene.2020.144846.

Bakhashab S, Filimban N, Altall RM, et al. The Effect Sizes of PPARγ rs1801282, FTO rs9939609, and MC4R rs2229616 Variants on Type 2 Diabetes Mellitus Risk among the Western Saudi Population: A Cross-Sectional Prospective Study. Genes (Basel). 2020;11(1):98. doi:10.3390/genes11010098.

Bala C, Craciun AE, Hancu N. Updating The Concept Of Metabolically Healthy Obesity. Acta Endocrinol (Buchar). 2016;12(2):197-205. doi:10.4183/aeb.2016.197.

Baldini G, Phelan KD. The melanocortin pathway and control of appetite-progress and therapeutic implications. J Endocrinol. 2019;241(1):R1-R33. doi:10.1530/JOE-18-0596.

Ben Ali S, Sediri Y, Kallel A, et al. The G3057A LEPR polymorphism is associated with obesity in Tunisian women. Nutr Metab Cardiovasc Dis. 2011;21(8):591-596. doi:10.1016/j.numecd.2009.12.011.

Berrington de Gonzalez A, Hartge P, Cerhan JR, et al. Body-mass index and mortality among 1.46 million white adults. N Engl J Med. 2010;363(23):2211-2219. doi:10.1056/NEJMoa1000367.

Berthold HK, Giannakidou E, Krone W, Mantzoros CS, Gouni-Berthold I. The Leu72Met polymorphism of the ghrelin gene is associated with a decreased risk for type 2 diabetes. Clin Chim Acta. 2009;399(1-2):112-116. doi:10.1016/j.cca.2008.09.022.

Bing C, Ambye L, Fenger M, et al. Large-scale studies of the Leu72Met polymorphism of the ghrelin gene in relation to the metabolic syndrome and associated quantitative traits. Diabet Med. 2005;22(9):1157-1160. doi:10.1111/j.1464-5491.2005.01575.x.

Blüher M. Metabolically Healthy Obesity. Endocr Rev. 2020;41(3):405-420. doi:10.1210/endrev/bnaa004.

Blüher M. The distinction of metabolically 'healthy' from 'unhealthy' obese individuals. Curr Opin Lipidol. 2010;21(1):38-43. doi:10.1097/MOL.0b013e3283346ccc.

Boumaiza I, Omezzine A, Rejeb J, et al. Relationship between leptin G2548A and leptin receptor Q223R gene polymorphisms and obesity and metabolic syndrome risk in Tunisian volunteers. Genet Test Mol Biomarkers. 2012;16(7):726-733. doi:10.1089/gtmb.2011.0324.

Brandão I, Martins MJ, Monteiro R. Metabolically Healthy Obesity-Heterogeneity in Definitions and Unconventional Factors. Metabolites. 2020;10(2):48. doi:10.3390/metabo10020048.

Breitfeld J, Kehr S, Müller L, et al. Developmentally Driven Changes in Adipogenesis in Different Fat Depots Are Related to Obesity. Front Endocrinol (Lausanne). 2020;11:138. doi:10.3389/fendo.2020.00138.

Candi E, Tesauro M, Cardillo C, et al. Metabolic profiling of visceral adipose tissue from obese subjects with or without metabolic syndrome. Biochem J. 2018;475(5):1019-1035. doi:10.1042/BCJ20170604.

Chait A, den Hartigh LJ. Adipose Tissue Distribution, Inflammation and Its Metabolic Consequences, Including Diabetes and Cardiovascular Disease. Front Cardiovasc Med. 2020;7:22. doi:10.3389/fcvm.2020.00022.

Childhood overweight and obesity. 2015. Available from: http://www.who.int/dietphysicalactivity/childhood/en/.

Chung S, Kim YJ, Yang SJ, Lee Y, Lee M. Nutrigenomic Functions of PPARs in Obesogenic Environments. PPAR Res. 2016;2016:4794576. doi:10.1155/2016/4794576.

Cristancho AG, Lazar MA. Forming functional fat: a growing understanding of adipocyte differentiation. Nat Rev Mol Cell Biol. 2011;12(11):722-734. doi:10.1038/nrm3198.

Crovesy L, Rosado EL. Interaction between genes involved in energy intake regulation and diet in obesity. Nutrition. 2019;67-68:110547. doi:10.1016/j.nut.2019.06.027.

da Fonseca ACP, Abreu GM, Zembrzuski VM, et al. The association of the fat mass and obesity-associated gene (FTO) rs9939609 polymorphism and the severe obesity in a Brazilian population. Diabetes Metab Syndr Obes. 2019;12:667-684. doi:10.2147/DMSO.S199542.

da Fonseca ACP, Abreu GM, Zembrzuski VM, et al. The association of the fat mass and obesity-associated gene (FTO) rs9939609 polymorphism and the severe obesity in a Brazilian population. Diabetes Metab Syndr Obes. 2019;12:667-684. doi:10.2147/DMSO.S199542.

Damanhoury S, Newton AS, Rashid M, Hartling L, Byrne JLS, Ball GDC. Defining metabolically healthy obesity in children: a scoping review. Obes Rev. 2018;19(11):1476-1491. doi:10.1111/obr.12721.

de Onis M, Blössner M, Borghi E. Global prevalence and trends of overweight and obesity among preschool children. Am J Clin Nutr. 2010;92(5):1257-1264. doi:10.3945/ajcn.2010.29786.

Després JP. Body fat distribution and risk of cardiovascular disease: an update. Circulation. 2012;126(10):1301-1313. doi:10.1161/CIRCULATIONAHA.111.067264.

Doaei S, Mosavi Jarrahi SA, Sanjari Moghadam A, et al. The effect of rs9930506 FTO gene polymorphism on obesity risk: a meta-analysis. Biomol Concepts. 2019;10(1):237-242. doi:10.1515/bmc-2019-0025.

Drucker DJ. Mechanisms of Action and Therapeutic Application of Glucagon-like Peptide-1. Cell Metab. 2018;27(4):740-756. doi:10.1016/j.cmet.2018.03.001.

Etemad A, Ramachandran V, Pishva SR, et al. Analysis of Gln223Agr polymorphism of Leptin Receptor Gene in type II diabetic mellitus subjects among Malaysians. Int J Mol Sci. 2013;14(9):19230-19244. doi:10.3390/ijms140919230.

Ferrara D, Montecucco F, Dallegri F, Carbone F. Impact of different ectopic fat depots on cardiovascular and metabolic diseases. J Cell Physiol. 2019;234(12):21630-21641. doi:10.1002/jcp.28821.

Gao C, Langefeld CD, Ziegler JT, et al. Genome-Wide Study of Subcutaneous and Visceral Adipose Tissue Reveals Novel Sex-Specific Adiposity Loci in Mexican Americans. Obesity (Silver Spring). 2018;26(1):202-212. doi:10.1002/oby.22074.

Gao L, Wang L, Yang H, Pan H, Gong F, Zhu H. MC4R Single Nucleotide Polymorphisms Were Associated with Metabolically Healthy and Unhealthy Obesity in Chinese Northern Han Populations. Int J Endocrinol. 2019;2019:4328909. doi:10.1155/2019/4328909.

Garfield AS, Li C, Madara JC, et al. A neural basis for melanocortin-4 receptor-regulated appetite. Nat Neurosci. 2015;18(6):863-871. doi:10.1038/nn.4011.

Gesta S, Bezy O, Mori MA, Macotela Y, Lee KY, Kahn CR. Mesodermal developmental gene Tbx15 impairs adipocyte differentiation and mitochondrial respiration. Proc Natl Acad Sci U S A. 2011;108(7):2771-2776. doi:10.1073/pnas.1019704108.

Gesta S, Blüher M, Yamamoto Y, et al. Evidence for a role of developmental genes in the origin of obesity and body fat distribution. Proc Natl Acad Sci U S A. 2006;103(17):6676-6681. doi:10.1073/pnas.0601752103.

Goossens GH, Blaak EE. Adipose tissue dysfunction and impaired metabolic health in human obesity: a matter of oxygen?. Front Endocrinol (Lausanne). 2015;6:55. doi:10.3389/fendo.2015.00055.

Gortan Cappellari G, Barazzoni R. Ghrelin forms in the modulation of energy balance and metabolism. Eat Weight Disord. 2019;24(6):997-1013. doi:10.1007/s40519-018-0599-6.

Hamer OW, Forstner D, Ottinger I, et al. The Pro115Gln polymorphism within the PPAR gamma2 gene has no epidemiological impact on morbid obesity. Exp Clin Endocrinol Diabetes. 2002;110(5):230-234. doi:10.1055/s-2002-33072.

Heid IM, Vollmert C, Hinney A, et al. Association of the 103I MC4R allele with decreased body mass in 7937 participants of two population based surveys. J Med Genet. 2005;42(4):e21. doi:10.1136/jmg.2004.027011.

Hill JH, Solt C, Foster MT. Obesity associated disease risk: the role of inherent differences and location of adipose depots. Horm Mol Biol Clin Investig. 2018;33(2):/j/hmbci.2018.33.issue-2/hmbci-2018-0012/hmbci-2018-0012.xml. doi:10.1515/hmbci-2018-0012.

Hosseini-Esfahani F, Koochakpoor G, Daneshpour MS, Sedaghati-Khayat B, Mirmiran P, Azizi F. Mediterranean Dietary Pattern Adherence Modify the Association between FTO Genetic Variations and Obesity Phenotypes. Nutrients. 2017;9(10):1064. doi:10.3390/nu9101064.

Iacobini C, Pugliese G, Blasetti Fantauzzi C, Federici M, Menini S. Metabolically healthy versus metabolically unhealthy obesity. Metabolism. 2019;92:51-60. doi:10.1016/j.metabol.2018.11.009.

Imaizumi T, Ando M, Nakatochi M, et al. Effect of dietary energy and polymorphisms in BRAP and GHRL on obesity and metabolic traits. Obes Res Clin Pract. 2018;12(Suppl 2):39-48. doi:10.1016/j.orcp.2016.05.004.

Jiang N, Li Y, Shu T, Wang J. Cytokines and inflammation in adipogenesis: an updated review. Front Med. 2019;13(3):314-329. doi:10.1007/s11684-018-0625-0.

Jiang Y, Mei H, Lin Q, et al. Interaction effects of FTO rs9939609 polymorphism and lifestyle factors on obesity indices in early adolescence. Obes Res Clin Pract. 2019;13(4):352-357. doi:10.1016/j.orcp.2019.06.004.

Joatar FE, Al Qarni AA, Ali ME, et al. Leu72Met and Other Intronic Polymorphisms in the GHRL and GHSR Genes Are Not Associated with Type 2 Diabetes Mellitus, Insulin Resistance, or Serum Ghrelin Levels in a Saudi Population. Endocrinol Metab (Seoul). 2017;32(3):360-369. doi:10.3803/EnM.2017.32.3.360.

Kahn CR, Wang G, Lee KY. Altered adipose tissue and adipocyte function in the pathogenesis of metabolic syndrome. J Clin Invest. 2019;129(10):3990-4000. doi:10.1172/JCI129187.

Karastergiou K, Fried SK, Xie H, et al. Distinct developmental signatures of human abdominal and gluteal subcutaneous adipose tissue depots. J Clin Endocrinol Metab. 2013;98(1):362-371. doi:10.1210/jc.2012-2953.

Karpe F, Pinnick KE. Biology of upper-body and lower-body adipose tissue--link to whole-body phenotypes. Nat Rev Endocrinol. 2015;11(2):90-100. doi:10.1038/nrendo.2014.185.

Kilpeläinen TO, Zillikens MC, Stančákova A, et al. Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile. Nat Genet. 2011;43(8):753-760. doi:10.1038/ng.866.

Kodama N, Tahara N, Tahara A, et al. Effects of pioglitazone on visceral fat metabolic activity in impaired glucose tolerance or type 2 diabetes mellitus. J Clin Endocrinol Metab. 2013;98(11):4438-4445. doi:10.1210/jc.2013-2920.

Komşu-Ornek Z, Demirel F, Dursun A, Ermiş B, Pişkin E, Bideci A. Leptin receptor gene Gln223Arg polymorphism is not associated with obesity and metabolic syndrome in Turkish children. Turk J Pediatr. 2012;54(1):20-24.

Kratz M, Coats BR, Hisert KB, et al. Metabolic dysfunction drives a mechanistically distinct proinflammatory phenotype in adipose tissue macrophages. Cell Metab. 2014;20(4):614-625. doi:10.1016/j.cmet.2014.08.010.

Lauria F, Siani A, Picó C, et al. A Common Variant and the Transcript Levels of MC4R Gene Are Associated With Adiposity in Children: The IDEFICS Study. J Clin Endocrinol Metab. 2016;101(11):4229-4236. doi:10.1210/jc.2016-1992.

Lee KY, Yamamoto Y, Boucher J, et al. Shox2 is a molecular determinant of depot-specific adipocyte function. Proc Natl Acad Sci U S A. 2013;110(28):11409-11414. doi:10.1073/pnas.1310331110.

Li J, Niu X, Li J, Wang Q. Association of PPARG Gene Polymorphisms Pro12Ala with Type 2 Diabetes Mellitus: A Meta-analysis. Curr Diabetes Rev. 2019;15(4):277-283. doi:10.2174/1573399814666180912130401.

Lin H, Zhang L, Zheng R, Zheng Y. The prevalence, metabolic risk and effects of lifestyle intervention for metabolically healthy obesity: a systematic review and meta-analysis: A PRISMA-compliant article. Medicine (Baltimore). 2017;96(47):e8838. doi:10.1097/MD.0000000000008838.

Liu L, Fan Q, Zhang F, et al. A Genomewide Integrative Analysis of GWAS and eQTLs Data Identifies Multiple Genes and Gene Sets Associated with Obesity. Biomed Res Int. 2018;2018:3848560. doi:10.1155/2018/3848560.

Liu P, Shi H, Huang C, et al. Association of LEP A19G polymorphism with cancer risk: a systematic review and pooled analysis. Tumour Biol. 2014;35(8):8133-8141. doi:10.1007/s13277-014-2088-5.

Loh NY, Minchin JEN, Pinnick KE, et al. RSPO3 impacts body fat distribution and regulates adipose cell biology in vitro. Nat Commun. 2020;11(1):2797. doi:10.1038/s41467-020-16592-z.

Lonardo A, Mantovani A, Lugari S, Targher G. Epidemiology and pathophysiology of the association between NAFLD and metabolically healthy or metabolically unhealthy obesity. Ann Hepatol. 2020;19(4):359-366. doi:10.1016/j.aohep.2020.03.001.

Makris MC, Alexandrou A, Papatsoutsos EG, et al. Ghrelin and Obesity: Identifying Gaps and Dispelling Myths. A Reappraisal. In Vivo. 2017;31(6):1047-1050. doi:10.21873/invivo.11168.

Manolopoulos KN, Karpe F, Frayn KN. Gluteofemoral body fat as a determinant of metabolic health. Int J Obes (Lond). 2010;34(6):949-959. doi:10.1038/ijo.2009.286.

McLaughlin T, Lamendola C, Coghlan N, et al. Subcutaneous adipose cell size and distribution: relationship to insulin resistance and body fat. Obesity (Silver Spring). 2014;22(3):673-680. doi:10.1002/oby.20209.

Mota de Sá P, Richard AJ, Hang H, Stephens JM. Transcriptional Regulation of Adipogenesis. Compr Physiol. 2017;7(2):635-674. doi:10.1002/cphy.c160022.

Neeland IJ, Ross R, Després JP, et al. Visceral and ectopic fat, atherosclerosis, and cardiometabolic disease: a position statement. Lancet Diabetes Endocrinol. 2019;7(9):715-725. doi:10.1016/S2213-8587(19)30084-1.

Parikh H, Groop L. Candidate genes for type 2 diabetes. Rev Endocr Metab Disord. 2004;5(2):151-176. doi:10.1023/B:REMD.0000021437.46773.26.

Peer N, Balakrishna Y, Durao S. Screening for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2020;5(5):CD005266. doi:10.1002/14651858.CD005266.pub2.

Perrini S, Ficarella R, Picardi E, et al. Differences in gene expression and cytokine release profiles highlight the heterogeneity of distinct subsets of adipose tissue-derived stem cells in the subcutaneous and visceral adipose tissue in humans. PLoS One. 2013;8(3):e57892. doi:10.1371/journal.pone.0057892.

Prastowo NA, Haryono IR. Elevated blood pressure and its relationship with bodyweight and anthropometric measurements among 8-11-year-old Indonesian school children. J Public Health Res. 2020;9(1):1723. doi:10.4081/jphr.2020.1723.

Rana S, Bhatti AA. Association and interaction of the FTO rs1421085 with overweight/obesity in a sample of Pakistani individuals. Eat Weight Disord. 2019;10.1007/s40519-019-00765-x. doi:10.1007/s40519-019-00765-x.

Reilly SM, Saltiel AR. Adapting to obesity with adipose tissue inflammation. Nat Rev Endocrinol. 2017;13(11):633-643. doi:10.1038/nrendo.2017.90.

Schleinitz D, Böttcher Y, Blüher M, Kovacs P. The genetics of fat distribution. Diabetologia. 2014;57(7):1276-1286. doi:10.1007/s00125-014-3214-z.

Speakman JR. The 'Fat Mass and Obesity Related' (FTO) gene: Mechanisms of Impact on Obesity and Energy Balance. Curr Obes Rep. 2015;4(1):73-91. doi:10.1007/s13679-015-0143-1.

Srivastava A, Mittal B, Prakash J, Narain VS, Natu SM, Srivastava N. Evaluation of MC4R [rs17782313, rs17700633], AGRP [rs3412352] and POMC [rs1042571] Polymorphisms with Obesity in Northern India. Oman Med J. 2014;29(2):114-118. doi:10.5001/omj.2014.28.

Stefan N, Häring HU, Cusi K. Non-alcoholic fatty liver disease: causes, diagnosis, cardiometabolic consequences, and treatment strategies. Lancet Diabetes Endocrinol. 2019;7(4):313-324. doi:10.1016/S2213-8587(18)30154-2.

Steinert RE, Feinle-Bisset C, Asarian L, Horowitz M, Beglinger C, Geary N. Ghrelin, CCK, GLP-1, and PYY(3-36): Secretory Controls and Physiological Roles in Eating and Glycemia in Health, Obesity, and After RYGB. Physiol Rev. 2017;97(1):411-463. doi:10.1152/physrev.00031.2014.

Sukhonthachit P, Aekplakorn W, Hudthagosol C, Sirikulchayanonta C. The association between obesity and blood pressure in Thai public school children. BMC Public Health. 2014;14:729. doi:10.1186/1471-2458-14-729.

Tang Y, Jin B, Zhou L, Lu W. MeQTL analysis of childhood obesity links epigenetics with a risk SNP rs17782313 near MC4R from meta-analysis. Oncotarget. 2017;8(2):2800-2806. doi:10.18632/oncotarget.13742.

Tatusova T, Ciufo S, Fedorov B, O'Neill K, Tolstoy I. RefSeq microbial genomes database: new representation and annotation strategy. Nucleic Acids Res. 2015;43(7):3872. doi:10.1093/nar/gkv278.

Tchkonia T, Giorgadze N, Pirtskhalava T, et al. Fat depot-specific characteristics are retained in strains derived from single human preadipocytes. Diabetes. 2006;55(9):2571-2578. doi:10.2337/db06-0540.

Tchkonia T, Lenburg M, Thomou T, et al. Identification of depot-specific human fat cell progenitors through distinct expression profiles and developmental gene patterns. Am J Physiol Endocrinol Metab. 2007;292(1):E298-E307. doi:10.1152/ajpendo.00202.2006.

Tsatsoulis A, Paschou SA. Metabolically Healthy Obesity: Criteria, Epidemiology, Controversies, and Consequences. Curr Obes Rep. 2020;9(2):109-120. doi:10.1007/s13679-020-00375-0.

Turcotte M, Abadi A, Peralta-Romero J, et al. Genetic contribution to waist-to-hip ratio in Mexican children and adolescents based on 12 loci validated in European adults. Int J Obes (Lond). 2019;43(1):13-22. doi:10.1038/s41366-018-0055-8.

Vecchié A, Dallegri F, Carbone F, et al. Obesity phenotypes and their paradoxical association with cardiovascular diseases. Eur J Intern Med. 2018;48:6-17. doi:10.1016/j.ejim.2017.10.020.

Vorotnikov AV, Stafeev IS, Menshikov MY, Shestakova MV, Parfyonova YV. Latent Inflammation and Defect in Adipocyte Renewal as a Mechanism of Obesity-Associated Insulin Resistance. Biochemistry (Mosc). 2019;84(11):1329-1345. doi:10.1134/S0006297919110099.

Vukovic R, Dos Santos TJ, Ybarra M, Atar M. Children With Metabolically Healthy Obesity: A Review. Front Endocrinol (Lausanne). 2019;10:865. doi:10.3389/fendo.2019.00865.

Wan R, Ding Z, Xia S, Zheng L, Lu J. Effects Of PPARγ2 Pro12Ala Variant On Adipocyte Phenotype Dependent Of DHA. Diabetes Metab Syndr Obes. 2019;12:2273-2279. doi:10.2147/DMSO.S214526.

Wang QA, Tao C, Gupta RK, Scherer PE. Tracking adipogenesis during white adipose tissue development, expansion and regeneration. Nat Med. 2013;19(10):1338-1344. doi:10.1038/nm.3324.

Xi B, Chandak GR, Shen Y, Wang Q, Zhou D. Association between common polymorphism near the MC4R gene and obesity risk: a systematic review and meta-analysis. PLoS One. 2012;7(9):e45731. doi:10.1371/journal.pone.0045731.

Yan J, Wang X, Tao H, Yang W, Luo M, Lin F. Lack of association between leptin G-2548A polymorphisms and obesity risk: Evidence based on a meta-analysis. Obes Res Clin Pract. 2015;9(4):389-397. doi:10.1016/j.orcp.2015.01.002.

Yang J, Loos RJ, Powell JE, et al. FTO genotype is associated with phenotypic variability of body mass index. Nature. 2012;490(7419):267-272. doi:10.1038/nature11401.

Yang LK, Tao YX. Biased signaling at neural melanocortin receptors in regulation of energy homeostasis. Biochim Biophys Acta Mol Basis Dis. 2017;1863(10 Pt A):2486-2495. doi:10.1016/j.bbadis.2017.04.010.

Yang X, Smith U. Adipose tissue distribution and risk of metabolic disease: does thiazolidinedione-induced adipose tissue redistribution provide a clue to the answer?. Diabetologia. 2007;50(6):1127-1139. doi:10.1007/s00125-007-0640-1.

You Y, Yu Y, Wu Y, et al. Association Study between Ghrelin Gene Polymorphism and Metabolic Syndrome in a Han Chinese Population. Clin Lab. 2017;63(1):175-181. doi:10.7754/Clin.Lab.2016.160715.

Yu K, Li L, Zhang L, Guo L, Wang C. Association between MC4R rs17782313 genotype and obesity: A meta-analysis. Gene. 2020;733:144372. doi:10.1016/j.gene.2020.144372.

Zatterale F, Longo M, Naderi J, et al. Chronic Adipose Tissue Inflammation Linking Obesity to Insulin Resistance and Type 2 Diabetes. Front Physiol. 2020;10:1607. doi:10.3389/fphys.2019.01607.

Zhao X, Yang Y, Sun BF, Zhao YL, Yang YG. FTO and obesity: mechanisms of association. Curr Diab Rep. 2014;14(5):486. doi:10.1007/s11892-014-0486-0.






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