Adipophilin increases triglyceride storage in human macrophages by stimulation of biosynthesis and inhibition of [beta]-oxidation

Lipid accumulation alters macrophage biology and contributes to lipid retention within the vessel wall. In this study, we investigated the role of adipophilin on triglyceride accumulation and lipid-droplet formation in THP-1-derived macrophages (THP-1 macrophages). In the presence of acetylated low-...

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Bibliographic Details
Published in:The FEBS journal 2006-08, Vol.273 (15), p.3498
Main Authors: Larigauderie, Guilhem, Cuaz-Pérolin, Clarisse, Younes, Amena B, Furman, Christophe, Lasselin, Catherine, Copin, Corinne, Jaye, Michael, Jean-Charles Fruchart, Rouis, Mustapha
Format: Article
Language:English
Subjects:
Adenoviruses
Cell culture
Cellular biology
Gene expression
Lipids
Proteins
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Summary:Lipid accumulation alters macrophage biology and contributes to lipid retention within the vessel wall. In this study, we investigated the role of adipophilin on triglyceride accumulation and lipid-droplet formation in THP-1-derived macrophages (THP-1 macrophages). In the presence of acetylated low-density lipoprotein, macrophages infected with an adenovirus expressing human adipophilin showed a 31% increase in triglyceride content and a greater number of lipid droplets compared with control cells. Incubation of macrophages with very low-density lipoprotein (VLDL) dramatically increased cellular triglyceride content similarly in control and adipophilin-overexpressing cells. By itself, VLDL increased adipophilin expression, which explains the lack of effect of adipophilin overexpression on cellular triglyceride content in macrophages loaded with VLDL. The lipid-droplet content of macrophages was increased by overexpression of adipophilin and/or loading with VLDL. In contrast, inhibition of adipophilin expression using siRNA prevented lipid-droplet formation and significantly reduced intracellular triglyceride content. Using inhibitors of Beta-oxidation and acyl-coenzyme A synthetase, results were obtained which suggest that adipophilin elevates cellular lipids by inhibition of Beta-oxidation and stimulation of long-chain fatty acid incorporation into triglycerides. Adipophilin expression in THP-1 macrophages altered the cellular content of different lipids and enhanced the size of lipid droplets, consistent with a role for adipophilin in human foam cell formation. [PUBLICATION ABSTRACT]
ISSN:1742-464X
1742-4658
DOI:10.1111/j.1742-4658.2006.05357.x