Lipodystrophy

Lipodystrophy study at UT Southwestern Medical Center is dedicated to the study, research, and therapy of human adipose tissue disorders. These pages provide an overview of the program, as well as information about the research team, therapies, enrolling in patient studies, and additional resources.

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 be secondary to various types of illnesses or drugs (acquired lipodystrophies).

Inherited Lipodystrophies

Inherited lipodystrophies are caused by mutations (alterations or blips) in a gene. Several genes responsible for inherited lipodystrophies have been identified.

Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by near total absence of fat tissue from birth. Homozygous or compound heterozygous mutations in four genes, 1-acylglycerol-3-phosphate-O-acyltransferase 2 (AGPAT2), Berardinelli-Seip congenital lipodystrophy 2 (BSCL2), caveolin 1 (CAV1), and Polymerase I and transcript release factor (PTRF; also known as cavin) are associated with the four subtypes of this disorder, CGL1, CGL2, CGL3, and CGL4 respectively.

Familial partial lipodystrophy (FPL) is mostly inherited as an autosomal dominant condition caused by heterozygous mutations in genes, such as, lamin A/ C (LMNA), peroxisome proliferator-activated receptor gamma (PPARG), and v-AKT murine thymoma oncogene homolog 2 (AKT2). Recently, a patient with autosomal recessive FPL has been identified with homozygous mutations in cell death –inducing Dffa-like effector C (CIDEC).

Recently, we reported patients with mandibular hypoplasia, deafness, and progeroid features (MDP syndrome). They have a few overlapping but some distinct clinical features as compared with classical MAD. The molecular basis of MDP syndrome remains to be determined.

We have also recently reported a novel autoinflammatory syndrome resulting in joint contractures, muscle atrophy, microcytic anemia, and panniculitis–induced lipodystrophy (JMP). The molecular genetic basis of this disorder remains to be determined.

Mandibuloacral dysplasia (MAD) associated lipodystrophy is an autosomal recessive condition with skeletal manifestations and partial or generalized lipodystrophy. Homozygous or compound heterozygous mutations in LMNA and zinc metalloproteinase (ZMPSTE24) genes have been linked to MAD.

The genetic basis of SHORT Syndrome, NPS, and some types of MAD remains to be determined.

Acquired 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 and results in APL. In a collaborative trial with the National Institutes of Health (NIH), 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.

To get more information on each of these types of lipodystrophy, and opportunities to participate in research with Dr. Garg, see Classifications. Funding for Dr. Garg's research on lipodystrophies comes from the National Institutes of Health (NIH) and the Clinical and Translational Research Center (CTRC).