Nutritional reprogramming of mouse liver proteome is dampened by metformin, resveratrol, and rapamycin.

Autor:	Le Couteur DG; Charles Perkins Centre, University of Sydney, NSW 2006, Australia; Centre for Education and Research on Ageing, Concord RG Hospital, NSW 2139, Australia; ANZAC Research Institute, Sydney, NSW 2139, Australia. Electronic address: david.lecouteur@sydney.edu.au., Solon-Biet SM; Charles Perkins Centre, University of Sydney, NSW 2006, Australia., Parker BL; Department of Anatomy and Physiology, University of Melbourne, VIC 3010, Australia., Pulpitel T; Charles Perkins Centre, University of Sydney, NSW 2006, Australia., Brandon AE; Charles Perkins Centre, University of Sydney, NSW 2006, Australia; School of Medical Sciences, University of Sydney, NSW 2006, Australia., Hunt NJ; Centre for Education and Research on Ageing, Concord RG Hospital, NSW 2139, Australia; ANZAC Research Institute, Sydney, NSW 2139, Australia., Wali JA; Charles Perkins Centre, University of Sydney, NSW 2006, Australia., Gokarn R; Charles Perkins Centre, University of Sydney, NSW 2006, Australia., Senior AM; Charles Perkins Centre, University of Sydney, NSW 2006, Australia., Cooney GJ; Charles Perkins Centre, University of Sydney, NSW 2006, Australia., Raubenheimer D; Charles Perkins Centre, University of Sydney, NSW 2006, Australia; School of Life and Environmental Science, University of Sydney, NSW 2006, Australia., Cogger VC; Centre for Education and Research on Ageing, Concord RG Hospital, NSW 2139, Australia; ANZAC Research Institute, Sydney, NSW 2139, Australia., James DE; Charles Perkins Centre, University of Sydney, NSW 2006, Australia; School of Life and Environmental Science, University of Sydney, NSW 2006, Australia., Simpson SJ; Charles Perkins Centre, University of Sydney, NSW 2006, Australia; School of Life and Environmental Science, University of Sydney, NSW 2006, Australia. Electronic address: stephen.simpson@sydney.edu.au.
Jazyk:	angličtina
Zdroj:	Cell metabolism [Cell Metab] 2021 Dec 07; Vol. 33 (12), pp. 2367-2379.e4. Date of Electronic Publication: 2021 Nov 11.
DOI:	10.1016/j.cmet.2021.10.016
Abstrakt:	Nutrient sensing pathways influence metabolic health and aging, offering the possibility that diet might be used therapeutically, alone or with drugs targeting these pathways. We used the Geometric Framework for Nutrition to study interactive and comparative effects of diet and drugs on the hepatic proteome in mice across 40 dietary treatments differing in macronutrient ratios, energy density, and drug treatment (metformin, rapamycin, resveratrol). There was a strong negative correlation between dietary energy and the spliceosome and a strong positive correlation between dietary protein and mitochondria, generating oxidative stress at high protein intake. Metformin, rapamycin, and resveratrol had lesser effects than and dampened responses to diet. Rapamycin and metformin reduced mitochondrial responses to dietary protein while the effects of carbohydrates and fat were downregulated by resveratrol. Dietary composition has a powerful impact on the hepatic proteome, not just on metabolic pathways but fundamental processes such as mitochondrial function and RNA splicing. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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