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Gut Microbial Fatty Acid Metabolites Reduce Triacylglycerol Levels in Hepatocytes
Author(s) -
Nanthirudjanar Tharnath,
Furumoto Hidehiro,
Zheng Jiawen,
Kim YoungIl,
Goto Tsuyoshi,
Takahashi Nobuyuki,
Kawada Teruo,
Park SiBum,
Hirata Akiko,
Kitamura Nahoko,
Kishino Shigenobu,
Ogawa Jun,
Hirata Takashi,
Sugawara Tatsuya
Publication year - 2015
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/s11745-015-4067-z
Subject(s) - lipogenesis , liver x receptor , fatty acid synthase , sterol regulatory element binding protein , fatty acid , biochemistry , chenodeoxycholic acid , fatty acid synthesis , chemistry , linoleic acid , gut flora , acetyl coa carboxylase , fatty liver , lipid metabolism , biology , medicine , sterol , cholesterol , pyruvate carboxylase , nuclear receptor , enzyme , transcription factor , gene , disease
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.