Gene-environment interactions in obesity.
Obesity is a global and growing problem. The detrimental health consequences of obesity are significant and include co-morbidities such as diabetes, cancer and coronary heart disease. The marked rise in obesity observed over the last three decades suggests that behavioural and environmental factors underpin the chronic mismatch between energy intake and energy expenditure. However, not all individuals become obese, suggesting that there is considerable variation in responsiveness to 'obesogenic' environments. Some individuals defend easily against a propensity to accumulate fat mass and become overweight whilst others are predisposed to gain weight, possibly as a function of genotype. The genetic contribution to obesity is well established. Common obesity is polygenic, involving complex gene-gene and gene-environment interactions, and it is these interactions that produce the multi-factorial obese phenotypes. Candidate gene variants for polygenic obesity appear to disrupt pathways involved in the regulation of energy intake and expenditure and include adrenergic receptors, uncoupling proteins, PPARG, POMC, MC4R and a set of single nucleotide polymorphisms in the FTO locus. Notably, the FTO gene is the most robust gene for common obesity characterised to date, and recent data shows that the FTO locus seems to confer risk of obesity through increasing energy intake and reduced satiety. Gene variants involved in pathways regulating addiction and reward behaviours may also play a role in predisposition to obesity. Understanding the routes through which the genotype is expressed will ultimately provide opportunities for developing strategies to intervene, as the interaction between genotype and environment is potentially modifiable through behaviour change.
Hetherington
Marion M
MM
Cecil
Joanne E
JE
D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D002149:Energy Intake / Q000235:genetics / Q000502:physiology*; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology*; D004777:Environment; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D009765:Obesity / Q000209:etiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics* / Q000378:metabolism
D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human