Watt 2021 Nat Commun
Watt KI, Henstridge DC, Ziemann M, Sim CB, Montgomery MK, Samocha-Bonet D, Parker BL, Dodd GT, Bond ST, Salmi TM, Lee RS, Thomson RE, Hagg A, Davey JR, Qian H, Koopman R, El-Osta A, Greenfield JR, Watt MJ, Febbraio MA, Drew BG, Cox AG, Porrello ER, Harvey KF, Gregorevic P (2021) Yap regulates skeletal muscle fatty acid oxidation and adiposity in metabolic disease. Nat Commun 12:2887. |
Watt KI, Henstridge DC, Ziemann M, Sim CB, Montgomery MK, Samocha-Bonet D, Parker BL, Dodd GT, Bond ST, Salmi TM, Lee RS, Thomson RE, Hagg A, Davey JR, Qian H, Koopman R, El-Osta A, Greenfield JR, Watt MJ, Febbraio MA, Drew BG, Cox AG, Porrello ER, Harvey KF, Gregorevic P (2021) Nat Commun
Abstract: Obesity is a major risk factor underlying the development of metabolic disease and a growing public health concern globally. Strategies to promote skeletal muscle metabolism can be effective to limit the progression of metabolic disease. Here, we demonstrate that the levels of the Hippo pathway transcriptional co-activator YAP are decreased in muscle biopsies from obese, insulin-resistant humans and mice. Targeted disruption of Yap in adult skeletal muscle resulted in incomplete oxidation of fatty acids and lipotoxicity. Integrated 'omics analysis from isolated adult muscle nuclei revealed that Yap regulates a transcriptional profile associated with metabolic substrate utilisation. In line with these findings, increasing Yap abundance in the striated muscle of obese (db/db) mice enhanced energy expenditure and attenuated adiposity. Our results demonstrate a vital role for Yap as a mediator of skeletal muscle metabolism. Strategies to enhance Yap activity in skeletal muscle warrant consideration as part of comprehensive approaches to treat metabolic disease.
β’ Bioblast editor: Reiswig R β’ O2k-Network Lab: AU Melbourne Bond S
Labels: MiParea: Respiration, Genetic knockout;overexpression
Pathology: Obesity
Organism: Mouse Tissue;cell: Skeletal muscle Preparation: Permeabilized tissue
Coupling state: LEAK, OXPHOS, ET
Pathway: F, N, S, NS, ROX
HRR: Oxygraph-2k
2021-08