Recent advances in understanding lipodystrophy: a focus on lipodystrophy-associated cardiovascular disease and potential effects of leptin therapy on cardiovascular function
Open Access
- 16 October 2019
- journal article
- review article
- Published by F1000 Research Ltd in F1000Research
- Vol. 8, 1756
- https://doi.org/10.12688/f1000research.20150.1
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.Funding Information
- American Heart Association (19EIA34760167)
- National Heart, Lung, and Blood Institute (1R01HL130301-01;1R01HL147639-01A1;, 1K99HL140139-01A1)
This publication has 99 references indexed in Scilit:
- Berardinelli-Seip Congenital Lipodystrophy 2/Seipin Is a Cell-Autonomous Regulator of Lipolysis Essential for Adipocyte DifferentiationMolecular and Cellular Biology, 2012
- Chemokine receptor CCR5: from AIDS to atherosclerosisBritish Journal of Pharmacology, 2011
- Lipodystrophy: pathophysiology and advances in treatmentNature Reviews Endocrinology, 2010
- Antiretrovirals Induce Endothelial Dysfunction via an Oxidant-Dependent Pathway and Promote Neointimal HyperplasiaToxicological Sciences, 2010
- Cardiomyopathy in Congenital and Acquired Generalized LipodystrophyMedicine, 2010
- Protein Tyrosine Phosphatase 1B, a Major Regulator of Leptin-Mediated Control of Cardiovascular FunctionJournal of the American College of Cardiology, 2009
- Genetic Evidence Supporting a Critical Role of Endothelial Caveolin-1 during the Progression of AtherosclerosisCell Metabolism, 2009
- Reexpression of caveolin-1 in endothelium rescues the vascular, cardiac, and pulmonary defects in global caveolin-1 knockout miceThe Journal of Experimental Medicine, 2007
- Mouse models of lipodystrophy: Key reagents for the understanding of the metabolic syndromeDrug Discovery Today: Disease Models, 2007
- Loss of Caveolae, Vascular Dysfunction, and Pulmonary Defects in Caveolin-1 Gene-Disrupted MiceScience, 2001