Behavioral susceptibility to obesity: Gene-environment interplay in the development of weight.

There is considerable evidence for both environmental and genetic causes of obesity. Increased availability of cheap, palatable food plays a role, but despite the ubiquity of the 'obesogenic' environment there is still substantial variation in weight - in fact, weight variability has gone up over recent decades. Twin and adoption studies show that adiposity is highly heritable (50-90%), and genome-wide association studies have started to identify single nucleotide polymorphisms (SNPs) associated with weight. We have proposed that genetic susceptibility to obesity is partly attributable to appetitive phenotypes, called the behavioral susceptibility theory (BST). BST proposes that individuals who inherit a more avid appetite or lower sensitivity to satiety are more likely to overeat in response to the food environment. Our laboratory has provided considerable evidence for BST using a variety of research approaches. We have used prospective epidemiological studies to demonstrate that appetite plays a causal role in the development of weight, twin designs to show that appetitive phenotypes are highly heritable and have genetic overlap with adiposity, and genomic analyses to show that obesity-related SNPs are associated with appetite and that appetite mediates some of the SNP-adiposity association. BST has helped to resolve the seeming paradox of both genetic determination and environmental determination of weight, and points to appetite as a useful target for pharmacological and behavioral interventions in the prevention and management of obesity.