Large-scale genetic study identifies genes that increase obesity risk while protecting against other metabolic diseases

Research Update

A new analysis of genetic datasets has revealed regions of the genome that are linked to both high levels of body fat and protection against some of the negative health effects of obesity. Obesity is a major risk factor for cardiometabolic diseases such as type 2 diabetes, heart disease and related conditions, and obese people tend to have unhealthy levels of glucose (sugar) and lipids in the blood and high blood pressure. But scientists have observed that up to 45% of obese people have healthy blood pressure and blood sugar/lipid levels, and are therefore not at high risk for diabetes and cardiovascular disease. The reasons why this group of people remain healthy have been poorly understood.

To determine if genetics may play a role, a team of researchers analyzed data from hundreds of thousands of people, mostly of European descent, who had previously been assessed for body fat and disease risk markers. They identified 62 regions of the genome that exhibit a seemingly paradoxical association of increased obesity risk and favorable effects on cardiometabolic outcomes. Genes identified in these regions point to both known and novel ways in which excess body fat may uncouple from cardiometabolic diseases. For example, some of these genes that increase body fat are associated with storing excess fat under the skin, as opposed to storing around internal organs where fat is metabolically harmful. Further analyzes have identified genes that are functionally involved in blood sugar enhancement, insulin signaling, fat cell regulation and development, and energy (calorie) expenditure. Additionally, genes have been identified that are linked to both increased body fat and changes in the nature of certain fatty tissues, from calorie-storing “white” fat to a form called “brown” fat. or “beige,” a process that can increase calorie burning and support a healthy metabolism. These findings help clarify the complex genetic underpinnings of obesity, and the identified genes may represent targets for new therapies aimed at reducing the cardiometabolic risk associated with excess body fat.

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