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Yap regulates skeletal muscle fatty acid oxidation and adiposity in metabolic disease


Watt, KI and Henstridge, DC and Ziemann, M and Sim, CB and Montgomery, MK and Samocha-Bonet, D and Parker, BL and Dodd, GT and Bond, ST and Salmi, TM and Lee, RS and Thomson, RE and Hagg, A and Davey, JR and Qian, H and Koopman, R and El-Osta, A and Greenfield, JR and Watt, MJ and Febbraio, MA and Drew, BG and Cox, AG and Porrello, ER and Harvey, KF and Gregorevic, P, Yap regulates skeletal muscle fatty acid oxidation and adiposity in metabolic disease, Nature Communications, 12, (1) pp. 1-14. ISSN 2041-1723 (2021) [Refereed Article]

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2021. The Authors. This article is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) License, (, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

DOI: doi:10.1038/s41467-021-23240-7


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.

Item Details

Item Type:Refereed Article
Keywords:skeletal muscle, metabolism, obesity, diabetes
Research Division:Biological Sciences
Research Group:Biochemistry and cell biology
Research Field:Cell metabolism
Objective Division:Health
Objective Group:Clinical health
Objective Field:Prevention of human diseases and conditions
UTAS Author:Henstridge, DC (Dr Darren Henstridge)
ID Code:144981
Year Published:2021
Web of Science® Times Cited:4
Deposited By:Health Sciences
Deposited On:2021-06-23
Last Modified:2021-09-09
Downloads:9 View Download Statistics

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