title: Anthocyanin inhibits high glucose-induced hepatic mtGPAT1 activation and prevents fatty acid synthesis through PKCζ.
abstract: Mitochondrial acyl-CoA:glycerol-sn-3-phosphate acyltransferase 1 (mtGPAT1) controls the first step of triacylglycerol (TAG) synthesis and is critical to the understanding of chronic metabolic disorders such as primary nonalcoholic fatty liver disease (NAFLD). Anthocyanin, a large group of polyphenols, was negatively correlated with hepatic lipid accumulation, but its impact on mtGPAT1 activity and NAFLD has yet to be determined. Hepatoma cell lines and KKAy mice were used to investigate the impact of anthocyanin on high glucose-induced mtGPAT1 activation and hepatic steatosis. Treatment with anthocyanin cyanidin-3-O-β-glucoside (Cy-3-g) reduced high glucose-induced GPAT1 activity through the prevention of mtGPAT1 translocation from the endoplasmic reticulum to the outer mitochondrial membrane (OMM), thereby suppressing intracellular de novo lipid synthesis. Cy-3-g treatment also increased protein kinase C ζ phosphorylation and membrane translocation in order to phosphorylate the mtF0F1-ATPase β-subunit, reducing its enzymatic activity and thus inhibiting mtGPAT1 activation. In vivo studies further showed that Cy-3-g treatment significantly decreases hepatic mtGPAT1 activity and its presence in OMM isolated from livers, thus ameliorating hepatic steatosis in diabetic KKAy mice. Our findings reveal a novel mechanism by which anthocyanin regulates lipogenesis and thereby inhibits hepatic steatosis, suggesting its potential therapeutic application in diabetes and related steatotic liver diseases.
authors.affiliation: Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University (Northern Campus), Guangzhou, Guangdong Province, PR China.
authors.forename: Honghui
authors.initials: H
authors.lastname: Guo
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Wenhua
authors.initials: W
authors.lastname: Ling
authors.forename: Xiang
authors.initials: X
authors.lastname: Feng
authors.forename: Min
authors.initials: M
authors.lastname: Xia
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000872:Anthocyanins / Q000494:pharmacology*; D015153:Blotting, Western; D004789:Enzyme Activation / Q000187:drug effects; D005227:Fatty Acids / Q000096:biosynthesis*; D005947:Glucose / Q000494:pharmacology*; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000378:metabolism; D051379:Mice; D011493:Protein Kinase C / Q000378:metabolism*; D006180:Proton-Translocating ATPases / Q000378:metabolism; D034622:RNA Interference
chemical_list: D000872:Anthocyanins; D005227:Fatty Acids; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D005992:Glycerol-3-Phosphate O-Acyltransferase; D011493:Protein Kinase C; D006180:Proton-Translocating ATPases; D005947:Glucose