Identifying Gene Variants Leading to Extreme Thinness as a Means to Develop Interventions for Obesity

Obesity has reached epidemic proportions in the United States: a staggering 35 percent of adults and 18 percent of children are obese. The condition not only poses significant health risks – such as an increased incidence of heart disease, diabetes, and cancer – but it is also a financial burden. People who are obese incur annual medical costs that are nearly $1,500 higher than those of normal weight. These statistics obviate an urgent need to address the obesity crisis.

A team led by Steven Hunt, Ph.D., a research professor in cardiovascular genetics, is searching for genes that lead to obesity resistance by examining families with a history of “healthy thinness”. People defined as thin and healthy have a low body mass index (BMI), and are free of unhealthy conditions or habits that lead to low body weight such as cancer, bulimia, anorexia, smoking, and drug use.

Studying obesity resistance genes in families with healthy thinness, as compared to studying genes that lead to obesity, has important advantages. Obesity can be caused by genetic effects, by habits or environmental factors - such as dietary intake and physical activity – or by a combination of influences, making it difficult to isolate people who are genetically predisposed to obesity. By contrast, healthy thinness is only minimally affected by habits and environmental factors. Healthy, thin individuals gain little weight, if any, despite their dietary and physical habits because of a genetic resistance to these influences.

The investigators have already identified and recruited individuals from 40 families with a history of healthy thinness. Next, they will sequence and compare the genomes of 40 thin subjects with those of 20 overweight subjects within the same families. Identification of obesity resistance genes and pathways that are present in thin subjects, and absent in overweight subjects, may translate to new ways of effectively treating or controlling obesity.