title: SREBP-1c overexpression induces triglycerides accumulation through increasing lipid synthesis and decreasing lipid oxidation and VLDL assembly in bovine hepatocytes.
abstract: The natural incidence of fatty liver in ruminants is significantly higher than in monogastric animals. Fatty liver is associated with sterol regulatory element-binding protein 1c (SREBP-1c). The aim of this study was to investigate the regulatory network effects of SREBP-1c on the lipid metabolic genes involved in fatty acid uptake, activation, oxidation, synthesis, and very low-density lipoprotein (VLDL) assembly in bovine hepatocytes. In vitro, bovine hepatocytes were transfected with an adenovirus-mediated SREBP-1c overexpression vector. SREBP-1c overexpression significantly up-regulated the expression and activity of the fatty acid uptake, activation, and synthesis enzymes: liver fatty acid binding protein, fatty acid translocase, acyl-CoA synthetase long-chain 1, acetyl-CoA carboxylase 1, and fatty acid synthase, increasing triglyceride (TG) synthesis and accumulation. SREBP-1c overexpression down-regulated the expression and activity of the lipid oxidation enzymes: carnitine palmitoyltransferase 1 and carnitine palmitoyltransferase 2. Furthermore, the apolipoprotein B100 expression and microsomal triglyceride transfer protein activity were significantly decreased. SREBP-1c overexpression reduced lipid oxidation and VLDL synthesis, thereby decreasing TG disposal and export. Therefore, large amounts of TG accumulated in the bovine hepatocytes. Taken together, these results indicate that SREBP-1c overexpression increases lipid synthesis and decreases lipid oxidation and VLDL export, thereby inducing TG accumulation in bovine hepatocytes.
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun 130062, Jilin, China.
authors.forename: Xinwei
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun 130062, Jilin, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun 130062, Jilin, China.
authors.forename: Wentao
authors.initials: W
authors.lastname: Yang
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun 130062, Jilin, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Xiao
authors.affiliation: Institute of Animal Science and Technology, Heilongjiang Bayi Agriculture University, Daqing 163319, Heilongjiang, China.
authors.forename: Shixin
authors.initials: S
authors.lastname: Fu
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun 130062, Jilin, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Deng
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun 130062, Jilin, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Ding
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun 130062, Jilin, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun 130062, Jilin, China. Electronic address: liuguowen2008@163.com.
authors.forename: Guowen
authors.initials: G
authors.lastname: Liu
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun 130062, Jilin, China. Electronic address: xbli@jlu.edu.cn.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002417:Cattle; D002478:Cells, Cultured; D005260:Female; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry*; D008079:Lipoproteins, VLDL / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D008055:Lipids; D008079:Lipoproteins, VLDL; D012333:RNA, Messenger; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides
keywords: Bovine hepatocytes; Lipid metabolism; Sterol regulatory element-binding protein 1c