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Gut Microbial Fatty Acid Metabolites Reduce Triacylglycerol Levels in Hepatocytes

  • Original Article
  • Published:
Lipids

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.

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Abbreviations

CLA:

Conjugated linoleic acids

CVD:

Cardiovascular disease

DMEM:

Dulbecco’s modified essential medium

EPA:

Eicosapentaenoic acid

FBS:

Fetal bovine serum

LA:

Linoleic acid

α-LNA:

α-Linolenic acid

LXRα:

Liver X receptor α

OA:

Oleic acid

PUFA:

Polyunsaturated fatty acids

RA:

Ricinoleic acid

SREBP-1c:

Sterol regulatory element binding protein-1c

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Acknowledgments

This research was partially supported by the Bio-Oriented Technology Research Advancement Institution of Japan to J. Ogawa. It was also partially supported by the NEDO Innovation Commercialization Venture Support Project with the collaboration of Nitto Pharmaceutical Industries, Ltd. and J. Ogawa.

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Authors and Affiliations

  1. Laboratory of Marine Bioproducts Technology, Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kyoto, 606-8502, Japan

    Tharnath Nanthirudjanar, Hidehiro Furumoto, Jiawen Zheng, Takashi Hirata & Tatsuya Sugawara

  2. Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, 611-0011, Japan

    Young-Il Kim, Tsuyoshi Goto, Nobuyuki Takahashi & Teruo Kawada

  3. Laboratory of Fermentation Physiology and Applied Microbiology, Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto, 606-8502, Japan

    Akiko Hirata, Nahoko Kitamura, Shigenobu Kishino & Jun Ogawa

  4. Laboratory of Industrial Microbiology, Graduate School of Agriculture, Kyoto University, Kyoto, 606-8502, Japan

    Si-Bum Park

  5. Shijonawate Gakuen University, Daito, 574-0011, Japan

    Takashi Hirata

Authors
  1. Tharnath Nanthirudjanar
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  2. Hidehiro Furumoto
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  3. Jiawen Zheng
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  4. Young-Il Kim
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  5. Tsuyoshi Goto
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  6. Nobuyuki Takahashi
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  7. Teruo Kawada
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  8. Si-Bum Park
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  9. Akiko Hirata
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  10. Nahoko Kitamura
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  11. Shigenobu Kishino
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  12. Jun Ogawa
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  13. Takashi Hirata
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  14. Tatsuya Sugawara
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Corresponding author

Correspondence to Tatsuya Sugawara.

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Nanthirudjanar, T., Furumoto, H., Zheng, J. et al. Gut Microbial Fatty Acid Metabolites Reduce Triacylglycerol Levels in Hepatocytes. Lipids 50, 1093–1102 (2015). https://doi.org/10.1007/s11745-015-4067-z

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  • DOI: https://doi.org/10.1007/s11745-015-4067-z

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