Systems-level analysis of insulin action in mouse strains provides insight into tissue- and pathway-specific interactions that drive insulin resistance.

Autor:	Nelson ME; School of Life and Environmental Sciences, University of Sydney, Camperdown, NSW 2006, Australia; Charles Perkins Centre, University of Sydney, Camperdown, NSW 2006, Australia., Madsen S; School of Life and Environmental Sciences, University of Sydney, Camperdown, NSW 2006, Australia; Charles Perkins Centre, University of Sydney, Camperdown, NSW 2006, Australia., Cooke KC; School of Life and Environmental Sciences, University of Sydney, Camperdown, NSW 2006, Australia; Charles Perkins Centre, University of Sydney, Camperdown, NSW 2006, Australia., Fritzen AM; School of Life and Environmental Sciences, University of Sydney, Camperdown, NSW 2006, Australia; Charles Perkins Centre, University of Sydney, Camperdown, NSW 2006, Australia., Thorius IH; School of Life and Environmental Sciences, University of Sydney, Camperdown, NSW 2006, Australia; Charles Perkins Centre, University of Sydney, Camperdown, NSW 2006, Australia., Masson SWC; School of Life and Environmental Sciences, University of Sydney, Camperdown, NSW 2006, Australia; Charles Perkins Centre, University of Sydney, Camperdown, NSW 2006, Australia., Carroll L; School of Life and Environmental Sciences, University of Sydney, Camperdown, NSW 2006, Australia; Charles Perkins Centre, University of Sydney, Camperdown, NSW 2006, Australia., Weiss FC; School of Life and Environmental Sciences, University of Sydney, Camperdown, NSW 2006, Australia; Charles Perkins Centre, University of Sydney, Camperdown, NSW 2006, Australia., Seldin MM; Department of Biological Chemistry and Center for Epigenetics and Metabolism, University of California, Irvine, Irvine, CA 92697, USA., Potter M; School of Life and Environmental Sciences, University of Sydney, Camperdown, NSW 2006, Australia; Charles Perkins Centre, University of Sydney, Camperdown, NSW 2006, Australia., Hocking SL; Charles Perkins Centre, University of Sydney, Camperdown, NSW 2006, Australia; Faculty of Medicine and Health, University of Sydney, Camperdown, NSW 2006, Australia., Fazakerley DJ; School of Life and Environmental Sciences, University of Sydney, Camperdown, NSW 2006, Australia; Charles Perkins Centre, University of Sydney, Camperdown, NSW 2006, Australia., Brandon AE; Charles Perkins Centre, University of Sydney, Camperdown, NSW 2006, Australia; Faculty of Medicine and Health, University of Sydney, Camperdown, NSW 2006, Australia., Thillainadesan S; School of Life and Environmental Sciences, University of Sydney, Camperdown, NSW 2006, Australia; Charles Perkins Centre, University of Sydney, Camperdown, NSW 2006, Australia., Senior AM; School of Life and Environmental Sciences, University of Sydney, Camperdown, NSW 2006, Australia; Charles Perkins Centre, University of Sydney, Camperdown, NSW 2006, Australia., Cooney GJ; Charles Perkins Centre, University of Sydney, Camperdown, NSW 2006, Australia; Faculty of Medicine and Health, University of Sydney, Camperdown, NSW 2006, Australia., Stöckli J; School of Life and Environmental Sciences, University of Sydney, Camperdown, NSW 2006, Australia; Charles Perkins Centre, University of Sydney, Camperdown, NSW 2006, Australia., James DE; School of Life and Environmental Sciences, University of Sydney, Camperdown, NSW 2006, Australia; Charles Perkins Centre, University of Sydney, Camperdown, NSW 2006, Australia; Faculty of Medicine and Health, University of Sydney, Camperdown, NSW 2006, Australia. Electronic address: david.james@sydney.edu.au.
Jazyk:	angličtina
Zdroj:	Cell metabolism [Cell Metab] 2022 Feb 01; Vol. 34 (2), pp. 227-239.e6. Date of Electronic Publication: 2022 Jan 11.
DOI:	10.1016/j.cmet.2021.12.013
Abstrakt:	Skeletal muscle and adipose tissue insulin resistance are major drivers of metabolic disease. To uncover pathways involved in insulin resistance, specifically in these tissues, we leveraged the metabolic diversity of different dietary exposures and discrete inbred mouse strains. This revealed that muscle insulin resistance was driven by gene-by-environment interactions and was strongly correlated with hyperinsulinemia and decreased levels of ten key glycolytic enzymes. Remarkably, there was no relationship between muscle and adipose tissue insulin action. Adipocyte size profoundly varied across strains and diets, and this was strongly correlated with adipose tissue insulin resistance. The A/J strain, in particular, exhibited marked adipocyte insulin resistance and hypertrophy despite robust muscle insulin responsiveness, challenging the role of adipocyte hypertrophy per se in systemic insulin resistance. These data demonstrate that muscle and adipose tissue insulin resistance can occur independently and underscore the need for tissue-specific interrogation to understand metabolic disease. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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