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Short-chain fatty acids as potential regulators of skeletal muscle metabolism and function

Abstract

A key metabolic activity of the gut microbiota is the fermentation of non-digestible carbohydrate, which generates short-chain fatty acids (SCFAs) as the principal end products. SCFAs are absorbed from the gut lumen and modulate host metabolic responses at different organ sites. Evidence suggests that these organ sites include skeletal muscle, the largest organ in humans, which plays a pivotal role in whole-body energy metabolism. In this Review, we evaluate the evidence indicating that SCFAs mediate metabolic cross-talk between the gut microbiota and skeletal muscle. We discuss the effects of three primary SCFAs (acetate, propionate and butyrate) on lipid, carbohydrate and protein metabolism in skeletal muscle, and we consider the potential mechanisms involved. Furthermore, we highlight the emerging roles of these gut-derived metabolites in skeletal muscle function and exercise capacity, present limitations in current knowledge and provide suggestions for future work.

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Fig. 1: Overview of the major metabolic pathways involved in the gut bacterial production of SCFAs.
Fig. 2: The effects of short-chain fatty acids on metabolic signalling pathways in skeletal muscle.
Fig. 3: The contribution of short-chain fatty acids to the gut–muscle axis.

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Acknowledgements

The Section for Nutrition Research is supported by the NIHR Biomedical Research Centre Funding Scheme. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. J.F. is funded by the Imperial College London President’s PhD Scholarship. E.S.C. dedicates this Review to the memory of Professor David A. Jones (1943–2020).

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J.F. and E.S.C. designed and conceived the outline of the Review. J.F., K.G.M., G.F. and E.S.C. wrote the manuscript.

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Correspondence to Edward S. Chambers.

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Frampton, J., Murphy, K.G., Frost, G. et al. Short-chain fatty acids as potential regulators of skeletal muscle metabolism and function. Nat Metab 2, 840–848 (2020). https://doi.org/10.1038/s42255-020-0188-7

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