Nature communications, 2021-06, Vol.12 (1), p.3377-3377, Article 3377
2021
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- Autor(en) / Beteiligte
- Titel
- Feeding diversified protein sources exacerbates hepatic insulin resistance via increased gut microbial branched-chain fatty acids and mTORC1 signaling in obese mice
- Ist Teil von
- Nature communications, 2021-06, Vol.12 (1), p.3377-3377, Article 3377
- Ort / Verlag
- London: Nature Publishing Group UK
- Erscheinungsjahr
- 2021
- Quelle
- EZB-FREE-00999 freely available EZB journals
- Beschreibungen/Notizen
- 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. Diet-induced changes in the microbiome have been associated with obesity. Here, using a mouse model, the authors show that a mixed protein source found in western diets exacerbates diet-induced obesity and insulin resistance by potentiating hepatic mTORC1/S6K1 signaling via microbial production of branched-chain fatty acids (BCFA).
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-021-23782-wTitel-ID: cdi_doaj_primary_oai_doaj_org_article_fd7e575509cd4ed1a49d204ec6f5f9de
- Format
- –
- Schlagworte
- 38/77, 45/23, 631/326/2565/2134, 631/443/319/1642, 64/60, 82/1, 90-kDa, adverse event, animal, Animal diseases, Animal Feed, animal food, Animal models, Animals, Biological Sciences, Biologiska vetenskaper, Casein, Cell Line, Chain branching, Diet, Dietary Proteins, Dietary Sucrose, disease model, Disease Models, Endocrinology and Diabetes, Endokrinologi och diabetes, fatty acid, Fatty Acids, fecal microbiota transplantation, Fecal microflora, feeding behavior, Gastrointestinal Microbiome, Germ-Free Life, germfree animal, gluconeogenesis, Hepatocytes, High-Fat, human, Humanities and Social Sciences, Humans, Insulin, Insulin resistance, Intestinal microflora, intestine flora, Life Sciences, lipid diet, Liver, liver cell, male, mammalian target of rapamycin complex 1, Mechanistic Target of Rapamycin Complex 1, metabolism, Mice, microbial activity, Microbiomes, Microbiota, Microorganisms, Mitochondria, mitochondrion, mouse, multidisciplinary, Obesity, Oxidation, pathology, physiology, protein, protein intake, Protein sources, Proteins, rat, Rats, Ribosomal Protein S6 Kinases, rodent, Rps6ka1 protein, S6 kinase, Science, Science (multidisciplinary), signal transduction, Signaling, sugar intake, Transplantation, Tumor, tumor cell line, Western, Western diet