Lipodystrophy: pathophysiology and advances in treatment

Abstract

Lipodystrophy is a medical condition characterized by complete or partial loss of adipose tissue. Not infrequently, lipodystrophy occurs in combination with pathological accumulation of adipose tissue at distinct anatomical sites. Patients with lipodystrophy exhibit numerous metabolic complications, which indicate the importance of adipose tissue as an active endocrine organ. Not only the total amount but also the appropriate distribution of adipose tissue depots contribute to the metabolic state. Genetic and molecular research has improved our understanding of the mechanisms underlying lipodystrophy. Circulating levels of hormones secreted by the adipose tissue, such as leptin and adiponectin, are greatly reduced in distinct subpopulations of patients with lipodystrophy. This finding rationalizes the use of these adipokines or of agents that increase their circulating levels, such as peroxisome proliferator-activated receptor γ (PPARγ) agonists, for therapeutic purposes. Other novel therapeutic approaches, including the use of growth hormone and growth-hormone-releasing factors, are also being studied as potential additions to the therapeutic armamentarium. New insights gained from research and clinical trials could potentially revolutionize the management of this difficult-to-treat condition.

Figure 1. Fat Redistribution in HIV-infected patients on HAART

A. Buffalo hump and increased abdominal adiposity in a patient with HALS. Courtesy of A.W. Karchmer, C.S. Mantzoros, and S. Tsiodras. Image from Leow et al, Copyright © 2003, The Endocrine Society. B. Loss of extremity fat and increased abdominal girth in a patient with HALS. Courtesy of A.W. Karchmer, C.S. Mantzoros, and S. Tsiodras. Image from Leow et al, Copyright © 2003, The Endocrine Society. C. Dual-energy x-ray absorptiometry (DEXA) scan indicating regions of interest for body composition analyses. Image from Grinspoon and Carr, Copyright © 2005 Massachusetts Medical Society. All rights reserved. D. Abdominal CT scan showing hepatomegaly in a patient with HALS. Courtesy of CS Mantzoros, Beth Israel Deaconess Medical Center (Boston, MA). Image from Leow et al, Copyright © 2003, The Endocrine Society. E. Change in truncal and limb fat over time in a patient with HALS. Truncal fat increases and limb fat decreases as a result of HAART. Leptin treatment commencing at week 13 begins to reverse pathological changes in fat distribution. Courtesy of C.S. Mantzoros.