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Molecular mechanisms of human lipodystrophies: from adipocyte lipid droplet to oxidative stress and lipotoxicity.
- Source :
-
The international journal of biochemistry & cell biology [Int J Biochem Cell Biol] 2011 Jun; Vol. 43 (6), pp. 862-76. Date of Electronic Publication: 2011 Mar 08. - Publication Year :
- 2011
-
Abstract
- Adipose tissue is now recognized for its major role in the control of energy metabolism and insulin sensitivity. We review here the human lipodystrophies, that are rare conditions in which total or partial fat loss is associated with severe lipid and glucose abnormalities leading to diabetes with early cardiovascular and hepatic complications. The genetic origin of a number of human lipodystrophies has been recently unraveled, emphasizing the importance of proteins of previously unknown or unexpected functions. Major adipose functions were also illuminated when studying acquired forms of lipodystrophies linked to human immunodeficiency virus-antiretrovirals. Overall, most of the proteins or functions affected by mutations or antiretrovirals result in altered adipogenesis and insulin sensitivity, triglyceride storage and formation of the unique adipocyte lipid droplet, oxidative stress and fat remodeling. Some mutations or antiretrovirals could affect directly (peroxisome proliferator-activated receptor-γ, Akt2) or indirectly (lamin A/C, human immunodeficiency virus-protease inhibitors) adipogenesis, through the transcription factors peroxisome proliferator-activated receptor gamma-γ or sterol regulatory element binding protein 1c, and insulin signaling through Akt2 that controls adipocyte lipolysis. A number of proteins mutated in genetic lipodystrophies are involved in the control of triglyceride synthesis towards the lipid droplet (1-acylglycerol-3-phosphate-O-acyltransferase 2), or its functions (seipin, cell death-inducing DFF45-like effector C, perilipin, caveolin-1, cavin-1). Decreased triglyceride storage leads to adipocyte lipotoxicity, mitochondrial dysfunction and increased oxidative stress, which could also be induced by some thymidine analogue antiretrovirals. This results in production of inflammatory mediators and deregulated release of free fatty acids. Thus, the impaired ability of adipose tissue to safely store triglycerides inside the lipid droplet results in impaired insulin sensitivity and adverted liver, muscles and heart functions leading to early complications.<br /> (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Subjects :
- Adipocytes pathology
Adipose Tissue pathology
Antiretroviral Therapy, Highly Active adverse effects
Humans
Inflammation
Insulin Resistance
Lipid Metabolism
Lipodystrophy chemically induced
Lipodystrophy genetics
Lipodystrophy pathology
Oxidative Stress
PPAR gamma genetics
PPAR gamma metabolism
Triglycerides metabolism
Adipocytes metabolism
Adipogenesis
Adipose Tissue metabolism
Lipodystrophy metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1878-5875
- Volume :
- 43
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- The international journal of biochemistry & cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 21392585
- Full Text :
- https://doi.org/10.1016/j.biocel.2011.03.002