Leptin in congenital and HIV-associated lipodystrophy.

Abstract

Leptin is a hormone secreted by adipocytes that regulates energy metabolism via peripheral action on glucose synthesis and utilization as well as through central regulation of food intake. Patients with decreased amounts of fat in their adipose tissue (lipoatrophy) will have low leptin levels, and hypoleptinemic states have been associated with a variety of metabolic dysfunctions. Pronounced complications of insulin resistance, dyslipidemia and fatty liver are observed in patients suffering from congenital or acquired generalized lipodystrophy while somewhat less pronounced abnormalities are associated with human immunodeficiency virus (HIV) and the use of highly active antiretroviral therapy, the so-called HIV-associated lipodystrophy. Previous uncontrolled open-label studies have demonstrated that physiological doses of leptin repletion have corrected many of the metabolic derangements observed in subjects with rare fat maldistribution syndromes such as generalized lipodystrophy. In the much more commonly encountered HIV-associated lipodystrophy, leptin replacement has been shown to decrease central fat mass and to improve insulin sensitivity, dyslipidemia, and glucose levels. The United States Food and Drug Administration has recently granted approval for recombinant leptin therapy for congenital and acquired generalized lipodystrophy, however large, well-designed, placebo-controlled studies are needed to assess long-term efficacy, safety and adverse effects of leptin replacement. In this review, we present the role of leptin in the metabolic complications of congenital and acquired lipodystrophy and discuss current and emerging clinical therapeutic uses of leptin in humans with lipodystrophy.

• Authors: Michael A Tsoukas, Olivia M Farr, Christos S Mantzoros
• Journal: Metabolism: clinical and experimental (Metabolism) Vol. 64 Issue 1 Pg. 47-59 (Jan 2015) ISSN: 1532-8600 [Electronic] United States
• PMID: 25267014 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Leptin

Topics

• Animals
• HIV-Associated Lipodystrophy Syndrome (drug therapy, metabolism)
• Humans
• Leptin (metabolism, pharmacology)
• Lipodystrophy (drug therapy, metabolism)
• Metabolic Diseases (drug therapy, metabolism)