Lipodystrophies are disorders of adipose tissue (fat) characterized by selective loss of fat from various parts of the body. 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 tissue. The extent of fat loss may determine the severity of metabolic complications related to insulin resistance, such as diabetes mellitus and high levels of serum triglycerides. Some patients may have only cosmetic problems while others may also have severe metabolic complications. These disorders can either be inherited (familial or genetic lipodystrophies) or can occur secondary to various types of illnesses or drugs (acquired lipodystrophies).

Inherited lipodystrophies are caused by mutations (alterations or blips) in a gene. Several genes responsible for different types of inherited lipodystrophies have been identified. These include AGPAT2 (1-acylglycerol-3-phosphate-O-acyltransferase 2), BSCL2 (Berardinelli-Seip congenital lipodystrophy 2) in Congenital Generalized Lipodystrophy (CGL), Lamin A/ C (LMNA), PPARG (peroxisome proliferator-activated receptor gamma), and genes in familial partial lipodystrophy. In addition, mutations in LMNA and ZMPSTE24 (zinc metalloproteinase) genes have been found to cause mandibuloacral dysplasia (MAD) associated lipodystrophy. Several other candidate genes are currently under investigation for other varieties of inherited lipodystrophies.

Acquired lipodystrophies are caused by medications, autoimmune mechanisms or other unknown mechanisms. These include highly active antiretroviral therapy (HAART) induced Lipodystrophy in HIV-infected patients (LD-HIV), Acquired Generalized Lipodystrophy (AGL), Acquired Partial Lipodystrophy (APL) and localized lipodystrophy. Acquired lipodystrophies do not have a direct genetic basis. Rather, many mechanisms may be involved. One such mechanism under investigation by Dr. Garg is an autoimmune response that destroys normal fat cells. We are currently investigating the underlying mechanisms for lipodystrophy in HIV-infected patients.

We are also studying various modes of therapy for HIV-patients with lipodystrophy. Significant progress is being made in investigating new modalities for the treatment of patients with lipodystrophies. In a recent collaborative trial with the National Institutes of Health, we showed that leptin-replacement therapy was beneficial for improving hyperglycemia (increased levels of blood sugar), hypertriglyceridemia (increased levels of blood lipids), insulin resistance (resistance to the action of hormone insulin) and fatty liver (accumulation of fat in the liver) in patients with lipodystrophy.

Using the navigation bar on the left, look under the classifications heading for more detailed information on each of these types of lipodystrophy. There are opportunities to participate in research studies with Dr. Garg and more information is available under the Research Efforts heading. Funding for Dr. Garg's research on the lipodystrophies comes from the National Institutes of Health (NIH) and the General Clinical Research Center (GCRC).