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Resveratrol enhances brown adipose tissue activity and white adipose tissue browning in part by regulating bile acid metabolism via gut microbiota remodeling

International Journal of Obesity volume 44, pages 1678–1690 (2020)Cite this article

Subjects

Abstract

Objective

Current evidence has linked dietary resveratrol (RSV) intake to the activation of brown adipose tissue (BAT) and induction of white adipose tissue (WAT) browning, which may be a potential means of improving glucose homeostasis. However, the underlying mechanisms remain unclear.

Methods

A diet containing RSV was fed to db/db mice for 10 weeks, following which the body weight, adipose tissue accumulation, bile acid (BA) profiles, and markers of BA metabolism were analyzed. Oral glucose tolerance testing, immunohistochemistry, and gut microbiota sequencing were also performed.

Results

RSV intervention improved glucose homeostasis in db/db mice, which was linked to the enhanced BAT activity and WAT browning. Moreover, RSV-treated mice exhibited altered plasma and fecal BA compositions and significant remodeling of the gut microbiota, the latter confirmed by a higher level of lithocholic acid (LCA) in the plasma and feces. LCA was identified to be the agonist of Takeda G-protein coupled receptor 5 (TGR5), which mediated the BAT activation and WAT browning by upregulating uncoupling protein 1 (UCP1) expression. Furthermore, depletion of the gut microbiota using antibiotics partially abolished the beneficial effects of RSV against glucose intolerance. Finally, microbiota transplantation experiments demonstrated that the RSV-induced beneficial effects were transferable, indicating that these effects were largely dependent on the gut microbiota.

Conclusions

These data indicate that RSV administration improves glucose homeostasis by enhancing BAT activation and WAT browning, a mechanism that might partially be mediated by the gut microbiota-BA-TGR5/UCP1 pathway.

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Fig. 1: RSV improves glucose homeostasis partially through enhancing the activation of BAT and the induction of WAT browning.
Fig. 2: RSV administration prevents obesity-driven dysbiosis.
Fig. 3: RSV treatment regulates bile acid metabolism.
Fig. 4: Gut microbiota contributes to the beneficial effects of RSV on BAT and IngWAT.
Fig. 5: Gut microbiota contributes to the beneficial effects of RSV on BAT and IngWAT.
Fig. 6: Illustration of the effect of RSV on glucose homeostasis mediated through the gut microbiota-bile acid-TGR5/UCP1 signaling pathway.

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Acknowledgements

The authors thank Changjun Zhao for assistance with animal tissue sample collection. This research was supported by project 81470562 of the National Natural Science Foundation of China (NSFC). The sequences reported in this paper have been deposited in the NCBI database (accession number PRJNA554960).

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Authors and Affiliations

  1. Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, 400038, Chongqing, People’s Republic of China

    Suocheng Hui, Yang Liu, Li Huang, Lin Zheng, Min Zhou, Hedong Lang, Xiaolan Wang, Long Yi & Mantian Mi

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Contributions

SH and LY, MM designed the experiments; SH, YL, LH, LZ, MZ, HL and XW performed the experiments; SH, YL, LH and XW analyzed the data; SH, LY, XW, LY and MM prepared the paper and had primary responsibility for final content. All authors read and approved the final paper.

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Correspondence to Long Yi or Mantian Mi.

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Hui, S., Liu, Y., Huang, L. et al. Resveratrol enhances brown adipose tissue activity and white adipose tissue browning in part by regulating bile acid metabolism via gut microbiota remodeling. Int J Obes 44, 1678–1690 (2020). https://doi.org/10.1038/s41366-020-0566-y

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