Genetic of obesity

Authors

  • Eduardo Cuestas Department of Pediatrics and Neonatology. Hospital Privado Centro Médico de Córdoba. Academic Unit. School of Medicine. National University of Cordoba. Argentina. Prof. Dr. E Cuestas. Servicio de Pediatría y Neonatología. Hospital Privado. Naciones Unidas 346 Córdoba X50016KEH. Telephone: +54-351-4688241. Fax: +54-351-4688286

DOI:

https://doi.org/10.31053/1853.0605.v65.n4.23569

Keywords:

obesity, genetics, child, adolescent

Abstract

Background: Obesity is a complex phenomenon that involves interactions between environmental and genetics factors. The genetic studies in animal models and humans has allowed great progress in the knowledge of body weight regulation. Identifying the hypothalamic leptin/melanocortin pathway as critical in many cases of monogenic obesity has permitted targeted, hypothesis-driven experiments to be performed, and has implicated new candidates as causative for previously uncharacterized clinical cases of obesity.
Data sources: Narrative review. PubMed, Lilacs and ScieLo databases were searched with the terms “obesity”, “genetics” and limited only for “ all child 0-18 years”.
Results: Numerous studies in children and adolescents, have tried to identify candidate genes. At present, the results are not conclusive. Thus, is yet premature genotype obese child on a large scale for predictive testing. Meanwhile, the effects of mutations in the melanocortin-4 receptor gene, for which the obese phenotype varies in the degree of severity among individuals, are now thought to be influenced by one's environmental surroundings. Molecular approaches have revealed that syndromes previously assumed to be controlled by a single gene are conversely regulated by multiple elements.
Conclusions: When specific treatments based on recent discoveries become available, genetic testing could help to discriminate different types of obesity that may respond differentially to therapeutic measures.

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References

Troiano RP, Flegal KM.Overweight children and adolescents: description,epidemiology, and demographics. Pediatrics 1998;101:497-504.

Flegal KM, Wei R, Ogden C Weight-for-stature compared with body mass index-for-age growth charts for the United States from the Centers for Disease Control and Prevention. Am J Clin Nutr 2002;75: 761-766.

Lunshof JE, Pirmohamed M, Gurwitz D. Personalized medicine: Decades away? Pharmacogenomics. 2006;7:237–241.

Hunter DJ. Gene-environment interactions in human diseases. Nat Rev Genet. 2005;6:287–298.

Mutch DM, Wahli W, Williamson G. Nutrigenomics and nutrigenetics: The emerging faces of nutrition. FASEB J. 2005;19:1602–1616.

Kaput J, Ordovas JM, Ferguson L, van Ommen B, Rodriguez RL, et al. The case for strategic international alliances to harness nutritional genomics for public and personal health. Br J Nutr. 2005;94:623–632.

Gorman C. Does my diet fit my genes? The new science of nutrigenomics has some answers. It explains why fat and caffeine are worse for some than others. Time. 2006;167:69–70.

Spiegelman BM, Flier JS. Obesity and the rgulation of energy balance. Cell 2001;104:531:543.

Barsh GS, Farooqi IS, O'Rahilly S. Genetics of body-weight regulation. Nature 2000;404: 644-651

Foufelle F, Ferré P.New perspectives in the regulation of hepatic glycolytic and lipogenic genes by insulin and glucose: a role for the transcription factor SREBP-1c. Biochem J 2002;366: 377-391

Ochoa MC, Marti A, Azcona C, Chueca M, Oyarzabal M, Pelach R, et al. Gene-gene interaction between PPAR gamma 2 and ADR beta 3 increases obesity risk in children and adolescents. Int J Obes Relat Metab Disord. 2004;28:S37–S41.

Argyropoulos G, Rankinen T, Neufeld DR, Rice T, Province MA, Leon AS, et al. A polymorphism in the human agouti-related protein is associated with late-onset obesity. J Clin Endocrinol Metab. 2002;87(9):4198–4202.

Martinez JA, Corbalan MS, Sanchez-Villegas A, Forga L, Marti A, Martinez-Gonzalez

MA. Obesity risk is associated with carbohydrate intake in women carrying the Gln27Glu beta2-adrenoceptor polymorphism. J Nutr. 2003;133:2549–2554.

Waterland RA, Garza C. Potential mechanisms of metabolic imprinting that lead to chronic disease. Am J Clin Nutr. 1999;69:179–197.

Gillman MW. Epidemiological challenges in studying the fetal origins of adult chronic disease. Int J Epidem. 2002;31:294–299.

Cuestas Montañés E, Achával Geraud A, Garcés Sardiña N, Larraya Bustos C.Waist circumference, dyslipidemia and hypertension in prepubertal children. An Pediatr (Barc). 2007;67:44-50

Hunter DJ. Gene-environment interactions in human diseases. Nat Rev Genet. 2005;6:287–298.

Mutch DM, Wahli W, Williamson G. Nutrigenomics and nutrigenetics: The emerging faces of nutrition. FASEB J. 2005;19:1602–1616.

Li G, Zhang Y, Wilsey JT, Scarpace PJ. Hypothalamic pro-opiomelanocortin gene delivery ameliorates obesity and glucose intolerance in aged rats. Diabetologia. 2005;48:2376–2385.

Seeley RJ, Burklow ML, Wilmer KA, Matthews CC, Reizes O, et al. The effect of the melanocortin agonist, MT-II, on the defended level of body adiposity. Endocrinology. 2005;146:3732–3738.

Molinoff PB, Shadiack AM, Earle D, Diamond LE, Quon CY. PT-141: A melanocortin agonist for the treatment of sexual dysfunction. Ann N Y Acad Sci. 2003;994:96–102.

Sebhat IK, Martin WJ, Ye Z, Barakat K, Mosley RT, et al. Design and pharmacology of N-[(3R)-1,2,3,4-tetrahydroisoquinolinium- 3-ylcarbonyl]-(1R)-1-(4-chlorobenzyl)- 2-[4-cyclohexyl-4-(1H-1,2,4-triazol- 1-ylmethyl)piperidin-1-yl]-2-oxoethylamine (1), a potent, selective, melanocortin subtype-4 receptor agonist. J Med Chem. 2002;45:4589–4593.

Wessells H, Hruby VJ, Hackett J, Han G, Balse-Srinivasan P, et al. MT-II induces penile erection via brain and spinal mechanisms. Ann N Y Acad Sci. 2003;994:90–95.

Chung WK, Leibel RL. Molecular physiology of syndromic obesities in humans. Trends Endocrinol Metab. 2005;16:267–272.

Goldstone AP. Prader-Willi syndrome: Advances in genetics, pathophysiology and treatment. Trends Endocrinol Metab. 2004;15:12–20.

Cummings DE, Clement K, Purnell JQ, Vaisse C, Foster KE, et al. Elevated plasma ghrelin levels in Prader-Willi syndrome. Nat Med. 2002;8:643–644.

Franzese A, Romano A, Spagnuolo MI, Ruju F, Valerio G. Growth hormone therapy in children with Prader-Willi syndrome. J Pediatr. 2006;148:846.

Carrel AL, Moerchen V, Myers SE, Bekx MT, Whitman BY, et al. Growth hormone improves mobility and body composition in infants and toddlers with Prader-Willi syndrome. J Pediatr. 2004;145:744–749.

Katsanis N, Lupski JR, Beales PL. Exploring the molecular basis of Bardet-Biedl syndrome. Hum Mol Genet. 2001;10:2293–2299.

Stoetzel C, Laurier V, Davis EE, Muller J, Rix S, et al. BBS10 encodes a vertebrate-specific chaperonin-like protein and is a major BBS locus. Nat Genet. 2006;38:521–524.

Nishimura DY, Swiderski RE, Searby CC, Berg EM, Ferguson AL, et al. Comparative genomics and gene expression analysis identifies BBS9, a new Bardet-Biedl syndrome gene. Am J Hum Genet. 2005;77:1021–1033.

Chiang AP, Beck JS, Yen HJ, Tayeh MK, Scheetz TE, et al. Homozygosity mapping with SNP arrays identifies TRIM32, an E3 ubiquitin ligase, as a Bardet-Biedl syndrome gene (BBS11). Proc Natl Acad Sci U S A. 2006;103:6287–6292.

Eichers ER, Lewis RA, Katsanis N, Lupski JR. Triallelic inheritance: A bridge between Mendelian and multifactorial traits. Ann Med. 2004;36:262–272.

Rankinen T, Perusse L, Weisnagel SJ, Snyder EE, Chagnon YC, Bouchard C 2002 The human obesity gene map: the 2001 update. Obes Res 10: 196-243

Clement K, Vaisse C, Lahlou N, Cabrol S, Pelloux V, Cassuto D, Gourmelen M, Dina C, Chambaz J, Lacorte JM, Basdevant A, Bougneres P, Lebouc Y, Froguel P, Guy-Grand B 1998 A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature 392: 398-401

Dubern B, Clement K, Pelloux V, Froguel P, Girardet JP, Guy-Grand B, Tounian P. Mutational analysis of melanocortin-4 receptor, agouti-related protein, and alpha-melanocyte-stimulating hormone genes in severely obese children. J Pediatr 2001;139: 204-209

Ardlie KG, Kruglyak L, Seielstad M. Patterns of linkage disequilibrium in the human genome. Nat Rev Genet. 2002;3:299–309.

Slavotinek AM, Searby C, Al-Gazali L, Hennekam RC, Schrander-Stumpel C, et al. Mutation analysis of the MKKS gene in McKusick-Kaufman syndrome and selected Bardet-Biedl syndrome patients. Hum Genet. 2002;110:561–567.

Fan Y, Esmail MA, Ansley SJ, Blacque OE, Boroevich K, et al. Mutations in a member of the Ras superfamily of small GTP-binding proteins causes Bardet-Biedl syndrome. Nat Genet. 2004;36:989–993.

Marshall WF, Nonaka S. Cilia: Tuning in to the cell's antenna. Curr Biol. 2006;16:R604–R614.

Mykytyn K, Mullins RF, Andrews M, Chiang AP, Swiderski RE, et al. Bardet-Biedl syndrome type 4 (BBS4)-null mice implicate Bbs4 in flagella formation but not global cilia assembly. Proc Natl Acad Sci U S A. 2004;101:8664–8669.

Mak HY, Nelson LS, Basson M, Johnson CD, Ruvkun G. Polygenic control of Caenorhabditis elegans fat storage. Nat Genet. 2006;38:363–368.

Roche HM, Phillips C, Gibney MJ. The metabolic syndrome: The crossroads of diet and genetics. Proc Nutr Soc. 2005;64:371–377.

Swarbrick MM, Vaisse C. Emerging trends in the search for genetic variants predisposing to human obesity. Curr Opin Clin Nutr Metab Care. 2003;6:369–375.

Hebebrand J, Friedel S, Schauble N, Geller F, Hinney A. Perspectives: Molecular genetic research in human obesity. Obes Rev. 2003;4:139–146.

Gallou-Kabani C, Junien C. Nutritional epigenomics of metabolic syndrome: New perspective against the epidemic. Diabetes. 2005;54:1899–1906.

Mager J, Bartolomei MS. Strategies for dissecting epigenetic mechanisms in the mouse. Nat Genet. 2005;37:1194–1200.

Mutch DM. Identifying regulatory hubs in obesity with nutrigenomics. Curr Opin Endocrinol Diabetes. 2006;13:431–437.

Laird NM, Lange C. Family-based designs in the age of large-scale gene-association studies. Nat Rev Genet. 2006;7:385–394.

Glazier AM, Nadeau JH, Aitman TJ. Finding genes that underlie complex traits. Science. 2002;298:2345–2349.

Slavotinek AM, Searby C, Al-Gazali L, Hennekam RC, Schrander-Stumpel C, et al. Mutation analysis of the MKKS gene in McKusick-Kaufman syndrome and selected Bardet-Biedl syndrome patients. Hum Genet. 2002;110:561–567.

Li S, Loss RJ. Progress in the genetics of common obesity: size matters. Curr Opin Lipidol 2008; 19(2):113-21.

Erikson JG. Epidemiology, genes and environment: lessons learned from the Helsinki birth cohort study. J Intern Med 2007;261:418-25.

Garruti G, Cotecchia S, Giampetruzzi F, Giorgino F, Giorgino R. Neuroendocrine deregulation of food intake, adipose tissue and gastrointestinal system in obesity and metabolic syndrome. J Gastrointest Liver Dis 2008;17(2):193-98.

Triana Hernández M, Ruiz Álvarez V. Obesity, a wordl epidemics.Genetic implications. Rev Cubana Invest Biomed 2007;26(2):1-10.

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Published

2019-02-26

How to Cite

1.
Cuestas E. Genetic of obesity. Rev Fac Cien Med Univ Nac Cordoba [Internet]. 2019 Feb. 26 [cited 2024 Jul. 29];65(4):117-24. Available from: https://revistas.unc.edu.ar/index.php/med/article/view/23569

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Literature Reviews