Like many other medical conditions, obesity is the result of an interplay between environmental and genetic factors.[1][2] Studies have identified variants in several genes that may contribute to weight gain and body fat distribution; although, only in a few cases are genes the primary cause of obesity.[3][4]
Polymorphisms in various genes controlling appetite and metabolism predispose to obesity under certain dietary conditions. The percentage of obesity that can be attributed to genetics varies widely, depending on the population examined, from 6% to 85%.[5] As of 2006, more than 41 sites on the human genome have been linked to the development of obesity when a favorable environment is present.[6] The involvement of genetic factors in the development of obesity is estimated to be 40–70%. Some of these obesogenic or leptogenic genes may influence the obese individual's response to weight loss or weight management.[7]
Although genetic deficiencies are currently considered rare, variations in these genes may predispose to common obesity.[9][10][11] Many candidate genes are highly expressed in the central nervous system.[12]
Several additional loci have been identified.[13] Also, several quantitative trait loci for BMI have been identified.
Adults who were homozygous for a particular FTOallele weighed about 3 kilograms more and had a 1.6-fold greater rate of obesity than those who had not inherited this trait.[18] This association disappeared, though, when those with FTO polymorphisms participated in moderately intensive physical activity equivalent to three to four hours of brisk walking.[19]
Some studies have focused upon inheritance patterns without focusing upon specific genes. One study found that 80% of the offspring of two obese parents were obese, in contrast to less than 10% of the offspring of two parents who were of normal weight.[27]
The thrifty gene hypothesis postulates that due to dietary scarcity during human evolution people are prone to obesity. Their ability to take advantage of rare periods of abundance by storing energy as fat would be advantageous during times of varying food availability, and individuals with greater adipose reserves would more likely survive famine. This tendency to store fat, however, would be maladaptive in societies with stable food supplies.[28] This is the presumed reason that Pima Native Americans, who evolved in a desert ecosystem, developed some of the highest rates of obesity when exposed to a Western lifestyle.[29]
Numerous studies of laboratory rodents provide strong evidence that genetics play an important role in obesity.[30][31]
The risk of obesity is determined by not only specific genotypes but also gene-gene interactions. However, there are still challenges associated with detecting gene-gene interactions for obesity.[32]
There are also genes that can be protective against obesity. For instance, in GPR75 variants were identified as such alleles in ~640,000 sequenced exomes which may be relevant to e.g. therapeutic strategies against obesity.[33][34] Other candidate anti-obesity-related genes include ALK,[35]TBC1D1,[36] and SRA1.[37]
The term "non-syndromic obesity" is sometimes used to exclude these conditions.[38] In people with early-onset severe obesity (defined by an onset before 10 years of age and body mass index over three standard deviations above normal), 7% harbor a single locus mutation.[39]
↑Skoblov, Mikhail; Andrey Marakhonov; Ekaterina Marakasova; Anna Guskova; Vikas Chandhoke; Aybike Birerdinc; Ancha Baranova (2013). "Protein partners of KCTD proteins provide insights about their functional roles in cell differentiation and vertebrate development". BioEssays. 35 (7): 586–596. doi:10.1002/bies.201300002. PMID23592240.
↑Meyre, David; Delplanque, Jérôme; Chèvre, Jean-Claude; Lecoeur, CéCile; Lobbens, StéPhane; Gallina, Sophie; Durand, Emmanuelle; Vatin, Vincent; et al. (18 January 2009). "Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populations". Nature Genetics. 41 (2): 157–9. doi:10.1038/ng.301. PMID19151714. S2CID11218794.
↑Steinberg, Gregory R.; Kemp, Bruce E.; Watt, Matthew J. (October 2007). "Adipocyte triglyceride lipase expression in human obesity". American Journal of Physiology. Endocrinology and Metabolism. 293 (4): E958–964. doi:10.1152/ajpendo.00235.2007. ISSN0193-1849. PMID17609260.
↑Kolata, Gina (2007). Rethinking thin: The new science of weight loss - and the myths and realities of dieting. Picador. p. 122. ISBN978-0-312-42785-6.
↑Chakravarthy MV, Booth FW (2004). "Eating, exercise, and "thrifty" genotypes: Connecting the dots toward an evolutionary understanding of modern chronic diseases". J. Appl. Physiol. 96 (1): 3–10. doi:10.1152/japplphysiol.00757.2003. PMID14660491.
↑Walley AJ, Asher JE, Froguel P (June 2009). "The genetic contribution to non-syndromic human obesity". Nat. Rev. Genet. 10 (7): 431–42. doi:10.1038/nrg2594. PMID19506576. S2CID10870369.