title: Activation of hepatic lipase expression by oleic acid: possible involvement of USF1.
abstract: 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.
authors.affiliation: Dept. Biochemistry, Cardiovascular Research School (COEUR), Erasmus MC, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. d.vandeursen@erasmusmc.nl
authors.forename: Diederik
authors.initials: D
authors.lastname: van Deursen
authors.forename: Marije
authors.initials: M
authors.lastname: van Leeuwen
authors.forename: Deniz
authors.initials: D
authors.lastname: Akdogan
authors.forename: Hadie
authors.initials: H
authors.lastname: Adams
authors.forename: Hans
authors.initials: H
authors.lastname: Jansen
authors.forename: Adrie J M
authors.initials: AJ
authors.lastname: Verhoeven
mesh_terms: D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D056945:Hep G2 Cells; D006801:Humans; D008049:Lipase / Q000235:genetics / Q000378:metabolism; D019301:Oleic Acid / Q000378:metabolism / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D051779:Sterol Regulatory Element Binding Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D051720:Upstream Stimulatory Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C504173:LIPC protein, human; D051779:Sterol Regulatory Element Binding Proteins; C497181:USF1 protein, human; D051720:Upstream Stimulatory Factors; D019301:Oleic Acid; D008049:Lipase