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-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.
Larigauderie
Guilhem
G
Inserm, U545, Lille, F-59019 France.
Cuaz-Pérolin
Clarisse
C
Younes
Amena B
AB
Furman
Christophe
C
Lasselin
Catherine
C
Copin
Corinne
C
Jaye
Michael
M
Fruchart
Jean-Charles
JC
Rouis
Mustapha
M
D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D017931:DNA Primers; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism*; D008565:Membrane Proteins; D010084:Oxidation-Reduction; D010455:Peptides / Q000502:physiology*; D000070780:Perilipin-2; D014280:Triglycerides / Q000378:metabolism*
D017931:DNA Primers; D008565:Membrane Proteins; C000602982:PLIN2 protein, human; D010455:Peptides; D000070780:Perilipin-2; D014280:Triglycerides