The Role of Genetics in the Pathophysiology of Obesity: A Systematic Review

Authors

  • Renata M. Pinto Department of Biology, Replicon Research Center, Catholic University of Goiás, Goiânia, GO, Brazil; Postgraduate Program in Genetics, Catholic University of Goiás, Goiânia, GO, Brazil; Health Sciences PhD Program, Federal University of Goiás, Goiânia, GO, Brazil; Department of Pediatrics, Federal University of Goiás, Goiânia, GO, Brazil
  • Lucas S. Steinmetz Department of Pediatrics, Federal University of Goiás, Goiânia, GO, Brazil
  • Julio M. G. Barbosa Department of Pediatrics, Federal University of Goiás, Goiânia, GO, Brazil
  • Arthur F. C. S. Mendes Department of Pediatrics, Federal University of Goiás, Goiânia, GO, Brazil
  • Maria P. Curado Department of Biology, Replicon Research Center, Catholic University of Goiás, Goiânia, GO, Brazil; Health Sciences PhD Program, Federal University of Goiás, Goiânia, GO, Brazil
  • Aparecido D. da Cruz Department of Biology, Replicon Research Center, Catholic University of Goiás, Goiânia, GO, Brazil; Postgraduate Program in Genetics, Catholic University of Goiás, Goiânia, GO, Brazil; Laboratory of Human Cytogenetics and Molecular Genetics, Secretary of State for Health of Goiás (LACEN/SESGO), Goiânia, GO, Brazil; Biotechnology and Biodiversity Graduate Program, University of Brasília, Brasília, DF, Brazil

DOI:

https://doi.org/10.17140/OROJ-6-137

Keywords:

Obesity; Genetics; Polygenic; Monogenic; Syndromic; Polymorphism

Abstract

Aim
The obesity epidemic has been largely attributed to changes in lifestyle habits established over the past three decades. These changes
are mainly attributed to excessive nutrition and decline in physical activity as well as additional factors such as reduced intestinal microbiota diversity, sleep duration, endocrine disruptors, and reduced variability of the ambient temperature. However, the obesogenic
environment is not sufficient to determine the presence of obesity, it is necessary that the lifestyle becomes associated with a personal
predisposition for the phenotype to emerge. In this article, we review the main forms of monogenic and syndromic obesity, as well as
a historical summary of the search for the genes that add up to confer greater risk for the development of polygenic obesity.
Methods
We carried out a PubMed search, along with ExcerptaMedica database (EMBASE)/Cochrane library, Web Sciences for the Medical
Subject Headings (MeSH) terms “obesity’’ AND “genetics” for the past 5-years.
Results
We found a total of 14057 articles pertaining to obesity and genetics together of which we selected 92 articles for this review after
getting articles after searching cross references.
Conclusion
Studies with twins and adopted children show that 55 to 80% of the variation of body mass index (BMI) is attributed to genetic factors. According to the genetic criteria, obesity can be classified as A) Monogenic - when a mutated gene is responsible for the phenotype; B) Syndromic - when a set of specific symptoms are present and a small group of genes is involved; usually the term is used to
describe obese patients with cognitive delay, dysmorphic features, organ-specific abnormalities, hyperphagia, and/or other signs of
hypothalamic dysfunction; C) Polygenic - also called “common” obesity, present in up to 95% of cases. Many genes add up to give a
greater risk to the individual, and if associated with some habits culminates in obesity. In spite of its great relevance, the search for the
genes that raise the risk of obesity has not been easy. It is still a challenge for the scientific community to separate the genetic element
from the environmental component in the etiology of this disease. Individuals more susceptible to excessive adiposity may carry risk
variants in the genes that influence appetite control, the regulation of cellular machinery, lipid metabolism and adipogenesis, the energy
expenditure, insulin signaling, and inflammation.

References

Engin A. The definition and prevalence of obesity and metabol-ic syndrome. In: Obesity and Lipotoxicity. New York, USA: Springer; 2017: 1-17.

Ng M, Fleming T, Robinson M, et al.. Global, regional, and na-tional prevalence of overweight and obesity in children and adults during 1980-2013: A systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014; 384(9945): 766-781. doi: 10.1016/S0140-6736(14)60460-8

O’Rahilly S, Farooqi IS. Human obesity: A heritable neurobe-havioral disorder that is highly sensitive to environmental condi-tions. Diabetes. 2008; 57: 2905-2910. doi: 10.2337/db08-0210

Ordovas JM, Corella D. Nutritional genomics. Annu Rev Ge-nomics Human Genet. 2004; 5: 71-118. doi: 10.1146/annurev.ge-nom.5.061903.180008

Schwartz MW, Randy JS, Lori MZ, et al. Obesity pathogenesis: An endocrinesociety scientific statement. Endocr Rev. 2017; 38(4): 267-296. doi: 10.1210/er.2017-00111

Pinto RM, Silva JVP, Monteiro GMC, de Resende RC, Clemente RD, de Souza CSB. Physical activity: Benefits for prevention and treatment of childhood obesity. J Child Obes. 2018; 3(S2-003:1-5). 1-6. doi: 10.21767/2572-5394.100058

Reddon H, Gueant JL, Meyre D. The importance of gene–en-vironment interactions in human obesity. Clin Sci (Lond). 2016; 130(18): 1571-1597. doi: 10.1042/CS20160221

Rohde K, Keller M, la Cour Poulsen L, Blüher M, Kovacs P, Böttcher Y. Genetics and epigenetics in obesity. Metabolism. 2019; 92: 37-50. doi: 10.1016/j.metabol.2018.10.007

Neel JV. Diabetes mellitus: A “thrifty” genotype rendered detri-mental by “progress”? Am J Hum Genet. 1962; 14: 353-362.

Wang SP, Yang H, Wu JW et al. Metabolism as a tool for un-derstanding human brain evolution: Lipid energy metabolism as an example. J Hum Evol. 2014; 77: 41-49. doi: 10.1016/j. jhev-ol.2014.06.013

Pinto RM, Cominetti C, da Cruz AD. Basic and genetic aspects of food intake control and obesity: Role of dopamin receptor D2 TAQIA polymorphism. Obes Res Open J. 2016; 2(4): 119-127. doi: 10.17140/OROJ-2-119

Speakman JR. A non adaptive scenario explaining the genetic predisposition to obesity: The “predation release” hypothesis. Cell Metab. 2007; 6(1): 5-12. doi: 10.1016/j.cmet.2007.06.004

Kaprio J, Pulkkinen L, Rose RJ. Genetic and environ-mental factors in health-related behaviours: Studies on fin-ish twins and twin families. Twin Res. 2002; 5: 366-371. doi: 10.1375/136905202320906101

Stunkard J, Foch TT, Hrubec Z. A twin study of human obesity. JAMA. 1986; 256: 51-54. doi: 10.1001/jama.1986.03380010055024

Herskind AM, McGue M, Sorensen TI, Harvald B. Sex and 16 Pinto RM, et al age specific assessment of genetic and environmental influences on body mass index in twins. Int J Obes Relat Metab Disord. 1996; 20: 106-113.

Pigeyre M, Meyre D. Monogenic obesity. In: Freemark MS, ed. Pediatric Obesity Etiology, Pathogenesis and Treatment. 2nd ed. New York, USA: Humana Press; 2018: 135-152. doi: 10.1007/978-3- 319-68192-4

Huvenne H, Dubern B, Clément K, Poitou C. Rare genetic forms of obesity: Clinical approach and current treatments in 2016. Obes Facts. 2016; 9: 158-173. doi: 10.1159/000445061

Martinez JA. Perspectives on personalizes nutrition for obesity. J Nutrigenet Nutrigenomics. 2014; 7: 1-3. doi: 10.1159/000365158

Bell CG, Walley AW, Froguel P. The genetics of human obesity. Nat Rev Genet. 2005; 6: 221-234. doi: 10.1038/nrg1556

Farooqi IS, O’Rahilly S. Monogenic obesity in humans. Annu Rev Med. 2005; 56: 443-458. doi: 10.1146/annurev. med.56.062904.144924

Irizarry KA, Haqq AM. Syndromic Obesity. In: Freemark MS, ed. Pediatric Obesity Etiology, Pathogenesis and Treatment. 2nd ed. New York, USA: Humana Press; 2018: 153-182. doi: 10.1007/978-3- 319-68192-4

Oussaada SM, van Galen KA, Cooima MI, et al. The patho-genesis of obesity. Metabolism. 2019; 92: 26-36. doi: 10.1016/j.me-tabol.2018.12.012

Walley AJ, Asher JE, Froguel P. The genetic contribution to non-syndromic human obesity. Nat Rev Genet. 2009; 10(1): 431- 442. doi: 10.1038/nrg2594

Böettcher Y, Korner A, Kovacs P, et al. Obesity genes: Implica-tion in childhood obesity. Pediatrics and Child Health. 2011; 22(1): 31-36. doi: 10.1016/j.paed.2011.08.009

Loos RJ. Recent progress in genetics of common obesity. Br J Clin Pharmacol. 2009; 68(6): 811-829. doi: 10.1111/j.1365- 2125.2009.03523.x

Pinto RM, Silva DM, Queiroz FJ, et al. Reward deficiency syn-drome in children: obesity and metabolic disorders are associated with the SNP TaqIA C32806T of the DRD2 gene. Obes Res Open J. 2015; 2(2): 64-72. doi: 10.17140/OROJ-2-111

Loos RJF. Genetic determinants of common obesity and their value in prediction. Best Pract Res Clin Endocrinol Metab. 2012; 26: 211-226. doi: 10.1016/j.beem.2011.11.003

Hinney A, Giuranna J. Polygenic Obesity. In: Freemark MS, ed. Pediatric Obesity Etiology, Pathogenesis and Treatment. 2nd ed. New York, USA: Humana Press; 2018: 183-202. doi: 10.1007/978-3- 319-68192-4 Systematic Review | Volume 6 | Number 1|

Shetty B, Shantaram M. Heritability of body weight: An evi-dence for obesity? Int. J. Pharm. Med. &Bio. 2014; 3(1): 15-20.

Saunders CL, Chiodini BD, Sham P, et al. Meta-analysis of genome-wide linkage studies in BMI and obesity. Obesity (Silver Spring). 2007; 15: 2263-2275. doi: 10.1038/oby.2007.269

Khera AV, Chaffin M, Wade KH, et al. Polygenic prediction of weight and obesity. Trajectories from birth to adulthood. Cell. 2019; 177: 587-596.e9. doi: 10.1016/j.cell.2019.03.028

Rankinen T, Zuberi A, Chagnon YC, et al. The human obe-sity gene map: The 2005 update. Obes Res. 2006; 14: 529-644. doi: 10.1038/oby.2006.71

Speliotes EK, Willer CJ, Berndt SI, et al. Association analy-ses of 249.769 individuals reveal 18 new loci associated with body mass index. Nat Genet. 2010; 42: 937-948. doi: 10.1038/ng.686

Comuzzie AG, Cole AS, Laston SL, et al. Novel genetic loci identified for the pathophysiology of chidhood obesity in the his-panic population. PLoS One. 2012; 7(12): e51954. doi: 10.1371/ journal.pone.0051954

Bradfield JP, Taal HR, Timpson NJ, et al. A genome-wide as-Submit your article to this journal | https://openventio.org/submit-manuscript/ Systematic Review | Volume 6 | Number 1| Pinto RM, et al sociation meta-analysis identifies new childhood obesity loci. Nat Genet. 2012; 44: 526-531. doi: 10.1038/ng.2247

Locke AE, Kahali B, Berndt SI, et al. Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015; 518(7538): 197-206. doi: 10.1038/nature14177

Burdge GC, Lillycrop KA. Nutrition, epigenetics and devel-opmental plasticity: Implications for understanding human dis-ease. Annu Rev Nutr. 2010; 30: 315-339. doi: 10.1146/annurev. nutr.012809.104751

Ma RC, Tutino GE, Lillycrop KA, Hanson MA, Tam WH. Maternal diabetes, gestational diabetes and the role of epigenetics in their long term effects on offspring. Prog Biophys Mol Biol. 2015; 118: 55-68. doi: 10.1016/j.pbiomolbio.2015.02.010

Parsons TJ, Power C, Manor O. Fetal and early life growth and body mass index from birth to early adulthood in1958 British cohort longitudinal study. BMJ. 2001; 323(7325): 1331-1335. doi: 10.1136/bmj.323.7325.1331

Herrera BM, Keildsona S, Lindgrena CM. Genetics and epi-genetics of obesity. Maturitas. 2011; 69: 41-49. doi: 10.1016/j.ma-turitas.2011.02.018

Downloads

Published

2019-08-04

How to Cite

Renata M. Pinto, Lucas S. Steinmetz, Julio M. G. Barbosa, Arthur F. C. S. Mendes, Maria P. Curado, & Aparecido D. da Cruz. (2019). The Role of Genetics in the Pathophysiology of Obesity: A Systematic Review. Obesity Research, 11–17. https://doi.org/10.17140/OROJ-6-137

Issue

Volume 6 Issue 1 2019

Section

Articles

License

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

All content published in Obesity Research (OR) is licensed under the Creative Commons Attribution 4.0 International License (CC BY 4.0). This license allows anyone to copy, distribute, transmit, and adapt the work — including for commercial purposes — provided appropriate credit is given to the original author(s) and source.

Most read articles by the same author(s)