Identification of Rev-erbα as a physiological repressor of apoC-III gene transcription1

• Main Authors: Eric Raspé, Hélène Duez, Anethe Mansén, Coralie Fontaine, Catherine Fiévet, Jean-Charles Fruchart, Bjorn Vennström, Bart Staels
• Format: Article
• Language: English
• Published: Elsevier 2002-12-01
• Series: Journal of Lipid Research
• Subjects: apolipoprotein C-III; triglycerides; nuclear receptors
• Online Access: http://www.sciencedirect.com/science/article/pii/S0022227520327462

Elevated serum levels of triglyceride-rich remnant lipoproteins (TRL) are a major risk factor predisposing a subject to atherosclerosis. Apolipoprotein C-III (apoC-III) is a major constituent of TRL that impedes triglyceride hydrolysis and remnant clearance and, as such, may exert pro-atherogenic activities. In the present study, transient cotransfection experiments in rat hepatocytes in primary culture and rabbit kidney RK13 cells demonstrated that overexpression of Rev-erbα specifically decreases basal and HNF-4 stimulated human apoC-III promoter activity. A Rev-erbα response element was mapped by promoter deletion, mutation analysis, and gel-shift experiments to a AGGTCA half-site located at position −23/−18 (downstream of the TATA box) in the apoC-III promoter. Finally, Rev-erbα-deficient mice displayed elevated serum and liver mRNA levels of apoC-III together with increased serum VLDL triglycerides.Taken together, our data identify Rev-erbα as a regulator of apoC-III gene expression, providing a novel, physiological role for this nuclear receptor in the regulation of lipid metabolism.