title: Gut Microbial Fatty Acid Metabolites Reduce Triacylglycerol Levels in Hepatocytes.
abstract: Hydroxy and oxo fatty acids were recently found to be produced as intermediates during gut microbial fatty acid metabolism. Lactobacillus plantarum produces these fatty acids from unsaturated fatty acids such as linoleic acid. In this study, we investigated the effects of these gut microbial fatty acid metabolites on the lipogenesis in liver cells. We screened their effect on sterol regulatory element binding protein-1c (SREBP-1c) expression in HepG2 cells treated with a synthetic liver X receptor α (LXRα) agonist (T0901317). The results showed that 10-hydroxy-12(Z)-octadecenoic acid (18:1) (HYA), 10-hydroxy-6(Z),12(Z)-octadecadienoic acid (18:2) (γHYA), 10-oxo-12(Z)-18:1 (KetoA), and 10-oxo-6(Z),12(Z)-18:2 (γKetoA) significantly decreased SREBP-1c mRNA expression induced by T0901317. These fatty acids also downregulated the mRNA expression of lipogenic genes by suppressing LXRα activity and inhibiting SREBP-1 maturation. Oral administration of KetoA, which effectively reduced triacylglycerol accumulation and acetyl-CoA carboxylase 2 (ACC2) expression in HepG2 cells, for 2 weeks significantly decreased Srebp-1c, Scd-1, and Acc2 expression in the liver of mice fed a high-sucrose diet. Our findings suggest that the hypolipidemic effect of the fatty acid metabolites produced by L. plantarum can be exploited in the treatment of cardiovascular diseases or dyslipidemia.
authors.affiliation: Laboratory of Marine Bioproducts Technology, Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kyoto, 606-8502, Japan.
authors.forename: Tharnath
authors.initials: T
authors.lastname: Nanthirudjanar
authors.affiliation: Laboratory of Marine Bioproducts Technology, Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kyoto, 606-8502, Japan.
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Furumoto
authors.affiliation: Laboratory of Marine Bioproducts Technology, Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kyoto, 606-8502, Japan.
authors.forename: Jiawen
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, 611-0011, Japan.
authors.forename: Young-Il
authors.initials: YI
authors.lastname: Kim
authors.affiliation: Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, 611-0011, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Goto
authors.affiliation: Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, 611-0011, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, 611-0011, Japan.
authors.forename: Teruo
authors.initials: T
authors.lastname: Kawada
authors.affiliation: Laboratory of Industrial Microbiology, Graduate School of Agriculture, Kyoto University, Kyoto, 606-8502, Japan.
authors.forename: Si-Bum
authors.initials: SB
authors.lastname: Park
authors.affiliation: Laboratory of Fermentation Physiology and Applied Microbiology, Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto, 606-8502, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Hirata
authors.affiliation: Laboratory of Fermentation Physiology and Applied Microbiology, Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto, 606-8502, Japan.
authors.forename: Nahoko
authors.initials: N
authors.lastname: Kitamura
authors.affiliation: Laboratory of Fermentation Physiology and Applied Microbiology, Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto, 606-8502, Japan.
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Kishino
authors.affiliation: Laboratory of Fermentation Physiology and Applied Microbiology, Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto, 606-8502, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Ogawa
authors.affiliation: Laboratory of Marine Bioproducts Technology, Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kyoto, 606-8502, Japan.|Shijonawate Gakuen University, Daito, 574-0011, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hirata
authors.affiliation: Laboratory of Marine Bioproducts Technology, Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kyoto, 606-8502, Japan. sugawara@kais.kyoto-u.ac.jp.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Sugawara
mesh_terms: D000818:Animals; D004032:Diet; D005227:Fatty Acids / Q000008:administration & dosage* / Q000378:metabolism; D000069196:Gastrointestinal Microbiome; D005786:Gene Expression Regulation / Q000187:drug effects; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000378:metabolism* / Q000382:microbiology; D006801:Humans; D006845:Hydrocarbons, Fluorinated; D048191:Lactiplantibacillus plantarum / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis; D051780:Sterol Regulatory Element Binding Protein 1 / Q000096:biosynthesis / Q000235:genetics; D013449:Sulfonamides; D014280:Triglycerides / Q000235:genetics / Q000378:metabolism*; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D005227:Fatty Acids; D006845:Hydrocarbons, Fluorinated; D012333:RNA, Messenger; D051780:Sterol Regulatory Element Binding Protein 1; D013449:Sulfonamides; D014280:Triglycerides; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
keywords: Acetyl-CoA carboxylase; Hydroxy fatty acid; Lipogenesis; Liver; Oxo fatty acid; Sterol regulatory element binding protein-1c