Recent advances in understanding lipodystrophy: a focus on lipodystrophy-associated cardiovascular disease and potential effects of leptin therapy on cardiovascular function

Abstract

Lipodystrophy is a disease characterized by a partial or total absence of adipose tissue leading to severe metabolic derangements including marked insulin resistance, type 2 diabetes, hypertriglyceridemia, and steatohepatitis. Lipodystrophy is also a source of major cardiovascular disorders which, in addition to hepatic failure and infection, contribute to a significant reduction in life expectancy. Metreleptin, the synthetic analog of the adipocyte-derived hormone leptin and current therapy of choice for patients with lipodystrophy, successfully improves metabolic function. However, while leptin has been associated with hypertension, vascular diseases, and inflammation in the context of obesity, it remains unknown whether its daily administration could further impair cardiovascular function in patients with lipodystrophy. The goal of this short review is to describe the cardiovascular phenotype of patients with lipodystrophy, speculate on the etiology of the disorders, and discuss how the use of murine models of lipodystrophy could be beneficial to address the question of the contribution of leptin to lipodystrophy-associated cardiovascular disease.