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Open AccessArticle

Activation of Hepatic Lipase Expression by Oleic Acid: Possible Involvement of USF1

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Dept. Biochemistry, Cardiovascular Research School (COEUR), Erasmus MC, PO Box 2040, 3000 CA Rotterdam, The Netherlands
2
Dept. Clinical Chemistry, Cardiovascular Research School (COEUR), Erasmus MC, PO Box 2040, 3000 CA Rotterdam, The Netherlands
*
Author to whom correspondence should be addressed.
Nutrients 2009, 1(2), 133-147; https://doi.org/10.3390/nu1020133
Received: 7 October 2009 / Accepted: 28 October 2009 / Published: 29 October 2009
(This article belongs to the Special Issue Foodomics 2009)
Polyunsaturated fatty acids affect gene expression mainly through peroxisome proliferator-activated receptors (PPARs) and sterol regulatory element binding proteins (SREBPs), but how monounsaturated fatty acids affect gene expression is poorly understood. In HepG2 cells, oleate supplementation has been shown to increase secretion of hepatic lipase (HL). We hypothesized that oleate affects HL gene expression at the transcriptional level. To test this, we studied the effect of oleate on HL promoter activity using HepG2 cells and the proximal HL promoter region (700 bp). Oleate increased HL expression and promoter activity 1.3–2.1 fold and reduced SREBP activity by 50%. Downregulation of SREBP activity by incubation with cholesterol+25-hydroxycholesterol had no effect on HL promoter activity. Overexpression of SREBP2, but not SREBP1, reduced HL promoter activity, which was effected mainly through the USF1 binding site at -307/-312. Oleate increased the nuclear abundance of USF1 protein 2.7 ± 0.6 fold, while USF1 levels were reduced by SREBP2 overexpression. We conclude that oleate increases HL gene expression via USF1. USF1 may be an additional fatty acid sensor in liver cells. View Full-Text
Keywords: monounsaturated fatty acids; sterol-responsive element binding protein SREBP2; upstream stimulatory factor USF1; LIPC; transcriptional regulation monounsaturated fatty acids; sterol-responsive element binding protein SREBP2; upstream stimulatory factor USF1; LIPC; transcriptional regulation
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Van Deursen, D.; Van Leeuwen, M.; Akdogan, D.; Adams, H.; Jansen, H.; Verhoeven, A.J.M. Activation of Hepatic Lipase Expression by Oleic Acid: Possible Involvement of USF1. Nutrients 2009, 1, 133-147.

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