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144981 - yap regulates skeletal muscle.pdf (3.16 MB)

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

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posted on 2023-05-21, 00:11 authored by Watt, KI, Darren HenstridgeDarren Henstridge, 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
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.

History

Publication title

Nature Communications

Volume

12

Article number

2887

Number

2887

Pagination

1-14

ISSN

2041-1723

Department/School

School of Health Sciences

Publisher

Nature Pub. Group

Place of publication

United Kingdom

Rights statement

© 2021. The Authors. This article is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) License, (https://creativecommons.org/licenses/by/4.0/), 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.

Repository Status

  • Open

Socio-economic Objectives

Prevention of human diseases and conditions; Treatment of human diseases and conditions; Expanding knowledge in the health sciences

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