HIV Lipodystrophy: Lessons from a Novel Metabolic Syndrome
Sponsored by The American Federation for Medical Research

Recent evidence demonstrates a novel metabolic syndrome among HIV-infected patients, including altered lipid metabolism, substrate flux, fat distribution and insulin resistance. Increased visceral adiposity and subcutaneous fat atrophy are most prominent. Significant progress has been made in recent years to understand this syndrome. Increased lipolysis and flux of fatty acids to the liver and muscle contribute to insulin resistance. Protease inhibitors have been shown to affect PPAR signaling, adipocyte differentiation and apoptosis. At the same time, NRTI’s, through inhibition of mitochondrial DNA polymerase gamma, impair fatty acid oxidation, resulting in lipid accumulation in both the liver and muscle, and repartitioning away from the subcutaneous compartment. Furthermore, reduction in critical cytokines, including adiponectin impairs fatty acid oxidation.

Recent data suggest significant clinical consequences of insulin resistance in HIV-infected patients including increased cardiovascular disease. Recent data also suggest potentially beneficial effects of insulin sensitizing agents, such as the thiazolidinediones, to increase adiponectin and subcutaneous adipogenesis, while inhibiting lipolysis and reducing hepatic and intramuscular fat accumulation.  The HIV lipodystrophy syndrome is a novel metabolic syndrome in which to understand the mechanisms of insulin resistance and fat redistribution. The proposed symposium will cover critical pathophysiologic mechanisms of altered lipid metabolism and nutrient trafficking, highlighting the most recent clinical and molecular data on the effects of protease inhibitors and nucleoside reverse transcriptase inhibitors on these processes.