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

Authors: Choi, BéatriceDaniel, NoémieHoude, Vanessa.; Ouellette, Adia; Marcotte, BrunoVarin, Thibaut; Vors, Cécile; Feutry, Perrine; Ilkayeva, Olga; Ståhlman, Marcus; St-Pierre, Philippe; Bäckhed, Fredrik; Tremblay, Angelo; Phillip J. White; Marette, André.
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.
Document Type: Article de recherche
Issue Date: 7 June 2021
Open Access Date: 15 June 2021
Document version: VoR
Creative Commons Licence: https://creativecommons.org/licenses/by/4.0
Permalink: http://hdl.handle.net/20.500.11794/69384
This document was published in: Nature Communications, Vol. 12 (1), 1-16 (2021)
Nature Publishing Group
Alternative version: 10.1038/s41467-021-23782-w
Collection:Articles publiés dans des revues avec comité de lecture

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