title: Exendin-4 regulates redox homeostasis in rats fed with high-fat diet.
abstract: Non-alcoholic fatty liver disease (NAFLD) is associated with increased plasma homocysteine level, which is caused by down-regulation of hepatic cystathionine beta-synthase (CBS) activity. CBS catalyzes the first step in the transsulfuration of homocysteine to cysteine, which contributes ∼50% of the cysteine required for hepatic biosynthesis of glutathione (GSH), the most abundant antioxidant in cells. As the glucagon-like peptide-1 (GLP-1) receptor agonists (e.g. exendin-4) effectively reverse hepatic steatosis, the effect of exendin-4 on both homocysteine and redox status was investigated in the livers of rats fed with high-fat diet (HFD). It was found that HFD down-regulated CBS protein expression, which was probably due to induction of rno-miR-376c expression in the liver. The level of GSH was markedly reduced, whereas the level of malonydialdehyde, an indicator of lipid peroxidation, was significantly increased in the livers of rats fed with HFD. Exendin-4 treatment increased hepatic CBS protein and GSH levels, and reduced malonydialdehyde level in hyperlipidemic rats. Our findings suggest that GLP-1 receptor agonists have beneficial effects on redox homeostasis in NAFLD.
authors.affiliation: Department of Biochemistry, Kunming Medical University, Kunming 650031, China.
authors.forename: Shiwei
authors.initials: S
authors.lastname: Niu
authors.affiliation: Department of Pathology, Yan'an Hospital, Kunming 650051, China.
authors.forename: Liqiong
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Biochemistry, Kunming Medical University, Kunming 650031, China.
authors.forename: Ming
authors.initials: M
authors.lastname: He
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Kunming Medical University, Kunming 650032, China shudeli006@vip.sina.com pengyunzhu0308@163.com.
authors.forename: Yunzhu
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Department of Biochemistry, Kunming Medical University, Kunming 650031, China shudeli006@vip.sina.com pengyunzhu0308@163.com.
authors.forename: Shude
authors.initials: S
authors.lastname: Li
mesh_terms: D000818:Animals; D003541:Cystathionine beta-Synthase / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat; D015536:Down-Regulation; D000077270:Exenatide; D005978:Glutathione / Q000378:metabolism; D006706:Homeostasis; D006710:Homocysteine / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000503:physiopathology; D010084:Oxidation-Reduction; D010455:Peptides / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014688:Venoms
chemical_list: D010455:Peptides; D012333:RNA, Messenger; D014688:Venoms; D006710:Homocysteine; D008315:Malondialdehyde; D000077270:Exenatide; D003541:Cystathionine beta-Synthase; D005978:Glutathione
keywords: cystathionine beta-synthase; exendin-4; homocysteine; microRNA; non-alcoholic fatty liver disease; redox homeostasis