2. Academic Validation
  3. Gut Microbial Fatty Acid Metabolites Reduce Triacylglycerol Levels in Hepatocytes

Gut Microbial Fatty Acid Metabolites Reduce Triacylglycerol Levels in Hepatocytes

  • Lipids. 2015 Nov;50(11):1093-102. doi: 10.1007/s11745-015-4067-z.
Tharnath Nanthirudjanar 1,  Hidehiro Furumoto 1,  Jiawen Zheng 1,  Young-Il Kim 2,  Tsuyoshi Goto 2,  Nobuyuki Takahashi 2,  Teruo Kawada 2,  Si-Bum Park 3,  Akiko Hirata 4,  Nahoko Kitamura 4,  Shigenobu Kishino 4,  Jun Ogawa 4,  Takashi Hirata 1 5,  Tatsuya Sugawara 6
Affiliations

Affiliations

  • 1 Laboratory of Marine Bioproducts Technology, Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kyoto, 606-8502, Japan.
  • 2 Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, 611-0011, Japan.
  • 3 Laboratory of Industrial Microbiology, Graduate School of Agriculture, Kyoto University, Kyoto, 606-8502, Japan.
  • 4 Laboratory of Fermentation Physiology and Applied Microbiology, Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto, 606-8502, Japan.
  • 5 Shijonawate Gakuen University, Daito, 574-0011, Japan.
  • 6 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.
PMID: 26399511 DOI: 10.1007/s11745-015-4067-z
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.

Keywords

Acetyl-CoA carboxylase; Hydroxy fatty acid; Lipogenesis; Liver; Oxo fatty acid; Sterol regulatory element binding protein-1c.

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