UT Southwestern researchers have received a $2.2 million grant from the National Institute of health to study lipodystrophies, rare body fat disorders associated with an increased prevalence in insulin resistance, diabetes, fatty liver and high triglyceride levels.

              “Even though lipodystrophies characterized by loss of body fat in the face, arms and legs, affect roughly one in 10 million people, the discovery of genes involved in these diseases will add to our understanding how obesity causes insulin resistance and other metabolic complications,” said Dr. Abhimanyu Garg, chief of nutrition and metabolic diseases. “These genes may play a major role in the development of fat cells and their function throughout life.”

            In 1999 the NIH granted $1.6 million to UT southwestern researcher to study the genetics and metabolic basis of inherited forms of lipodystrophies.

            UT southwestern researchers have identified two of the four known genes involved in causing two forms of lipodystrophies, congenital generalized lipodystrophy – extreme lack of body fat at birth – and familial partial lipodystrophy – partial loss of fat from the arms and legs, which occur later in life.

           Dr. Garg and his collaborators will use the latest grant to take a closer look into how a specific gene, AGPAT 2, which forms a key enzyme involved in synthesizing fat in the body, causes lack of body fat and metabolic complications. The researchers will study a knockout mouse model, which lacks the AGPAT2 gene. The research may lead to new information about obesity and obesity-related diseases, including the metabolic syndrome related to insulin resistance.

              There are several different types of lipodystrophies and the degree of fat loss may vary from very small, depressed areas to near complete absence of adipose, or fat, tissue. The extent of fat loss usually determines the severity of metabolic complications related to insulin resistance, such as diabetes mellitus and high levels of serum triglycerides, said Dr. Garg, who has been studying patients with lipodystrophy for the past 16 years.

          “The identification of additional genes causing lipodystrophies may lead us to understand why individuals with apple-shaped obesity versus pear-shaped obesity have a stronger predisposition for heart disease and diabetes” said Dr. Garg, a senior investigator in the Center for Human Nutrition and holder of the Endowed chair in Human Nutrition.