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Original research
Myristoleic acid produced by enterococci reduces obesity through brown adipose tissue activation
  1. Lin-Hu Quan1,
  2. Chuanhai Zhang2,
  3. Meng Dong2,3,
  4. Jun Jiang1,
  5. Hongde Xu4,
  6. Chunlong Yan1,
  7. Xiaomeng Liu5,
  8. Huiqiao Zhou2,3,
  9. Hanlin Zhang2,3,
  10. Li Chen2,3,
  11. Fei-Liang Zhong1,
  12. Zhao-Bo Luo6,
  13. Sin-Man Lam7,
  14. Guanghou Shui7,
  15. Donghao Li1,
  16. Wanzhu Jin2,3
  1. 1 Key Laboratory of Natural Resource of the Changbai Mountain and Functional Molecular, Ministry of Education, Agricultural College, Yanbian University, Yanji, China
  2. 2 Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
  3. 3 Savaid Medical School, University of the Chinese Academy of Sciences, Beijing, China
  4. 4 School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
  5. 5 Institute of Neuroscience and Translational Medicine, College of Life Science and Agronomy, Zhoukou Normal University, Zhoukou, Henan, China
  6. 6 Jilin Provincial Key Laboratory of Transgenic Animal and Embryo Engineering, Yanbian University, Yanji, China
  7. 7 State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
  1. Correspondence to Professor Wanzhu Jin, Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, Beijing, China; jinw{at}ioz.ac.cn; Professor Donghao Li, Key Laboratory of Natural Resources of Changbai Mountain and Functional Molecules, Ministry of Education, Yanbian University, Yanji 133002, China; dhli{at}ybu.edu.cn

Abstract

Objective Dietary fibre has beneficial effects on energy metabolism, and the majority of studies have focused on short-chain fatty acids produced by gut microbiota. Ginseng has been reported to aid in body weight management, however, its mechanism of action is not yet clear. In this study, we focused on the potential modulating effect of ginseng on gut microbiota, aiming to identify specific strains and their metabolites, especially long-chain fatty acids (LCFA), which mediate the anti-obesity effects of ginseng.

Design Db/db mice were gavaged with ginseng extract (GE) and the effects of GE on gut microbiota were evaluated using 16S rDNA-based high throughput sequencing. To confirm the candidate fatty acids, untargeted metabolomics analyses of the serum and medium samples were performed.

Results We demonstrated that GE can induce Enterococcus faecalis, which can produce an unsaturated LCFA, myristoleic acid (MA). Our results indicate that E. faecalis and its metabolite MA can reduce adiposity by brown adipose tissue (BAT) activation and beige fat formation. In addition, the gene of E. faecalis encoding Acyl-CoA thioesterases (ACOTs) exhibited the biosynthetic potential to synthesise MA, as knockdown (KD) of the ACOT gene by CRISPR-dCas9 significantly reduced MA production. Furthermore, exogenous treatment with KD E. faecalis could not reproduce the beneficial effects of wild type E. faecalis, which work by augmenting the circulating MA levels.

Conclusions Our results demonstrated that the gut microbiota-LCFA-BAT axis plays an important role in host metabolism, which may provide a strategic advantage for the next generation of anti-obesity drug development.

  • obesity
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Footnotes

  • L-HQ, CZ, MD, JJ, HX and CY contributed equally.

  • Correction notice This article has been corrected since it published Online First. A second co-corresponding author has been added.

  • Contributors WJ, L-HQ, CZ, MD and DL. designed the research and analysed all of the results; L-HQ, JJ, HX and CY performed animal studies; CZ performed cellular experiments and animal tissue analysis; MD performed animal tissue analysis and bacteria dCas9 construction; XL, HZhou, HZhang, LC, Z-BL and F-LZ performed animal tissue analysis and whole-body animal imaging; S-ML and GS performed lipidomics analysis; and L-HQ, CZ, MD and WJ wrote the paper.

  • Funding This work was supported by the strategic priority research program (XDB13030000 to WJ), National Natural Science Foundation of China (31171131 and 81370951 to WJ, 81660643 to LQ), National Key Research and Development Program of China (2017YFC1001003 to WJ).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval All animal studies were approved by the In- stitutional Animal Care and Use Committee of Institute of Zoology (Chinese Academy of Sciences).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available in a public, open access repository. Data are available upon reasonable request.

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