Feeding diversified protein sources exacerbates hepatic insulin resistance via increased gut microbial branched-chain fatty acids and mTORC1 signaling in obese mice

Béatrice S.-Y. Choi, Noëmie Daniel, Vanessa P. Houde, Adia Ouellette, Bruno Marcotte, Thibault V. Varin, Cécile Vors, Perrine Feutry, Olga Ilkayeva, Marcus Ståhlman, Philippe St-Pierre, Fredrik Bäckhed, Angelo Tremblay, Phillip J. White and André Marette ()
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Béatrice S.-Y. Choi: Université Laval
Noëmie Daniel: Université Laval
Vanessa P. Houde: Université Laval
Adia Ouellette: Université Laval
Bruno Marcotte: Université Laval
Thibault V. Varin: Université Laval
Cécile Vors: Université Laval
Perrine Feutry: Université Laval
Olga Ilkayeva: Duke University
Marcus Ståhlman: University of Gothenburg
Philippe St-Pierre: Université Laval
Fredrik Bäckhed: University of Gothenburg
Angelo Tremblay: Université Laval
Phillip J. White: Duke University
André Marette: Université Laval

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: Abstract Animal models of human diseases are classically fed purified diets that contain casein as the unique protein source. We show that provision of a mixed protein source mirroring that found in the western diet exacerbates diet-induced obesity and insulin resistance by potentiating hepatic mTORC1/S6K1 signaling as compared to casein alone. These effects involve alterations in gut microbiota as shown by fecal microbiota transplantation studies. The detrimental impact of the mixed protein source is also linked with early changes in microbial production of branched-chain fatty acids (BCFA) and elevated plasma and hepatic acylcarnitines, indicative of aberrant mitochondrial fatty acid oxidation. We further show that the BCFA, isobutyric and isovaleric acid, increase glucose production and activate mTORC1/S6K1 in hepatocytes. Our findings demonstrate that alteration of dietary protein source exerts a rapid and robust impact on gut microbiota and BCFA with significant consequences for the development of obesity and insulin resistance.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23782-w

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DOI: 10.1038/s41467-021-23782-w

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