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

Watt, KI, Henstridge, DC, Ziemann, Mark, 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 and Gregorevic, P 2021, Yap regulates skeletal muscle fatty acid oxidation and adiposity in metabolic disease, Nature communications, vol. 12, no. 1, pp. 1-14, doi: 10.1038/s41467-021-23240-7.

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Title Yap regulates skeletal muscle fatty acid oxidation and adiposity in metabolic disease
Author(s) Watt, KI
Henstridge, DC
Ziemann, MarkORCID iD for Ziemann, Mark orcid.org/0000-0002-7688-6974
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
Journal name Nature communications
Volume number 12
Issue number 1
Article ID 2887
Start page 1
End page 14
Total pages 14
Publisher Nature Publishing Group
Place of publication London, Eng.
Publication date 2021
ISSN 2041-1723
2041-1723
Keyword(s) cell biology
metabolism
Summary 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.
Language eng
DOI 10.1038/s41467-021-23240-7
Indigenous content off
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Free to Read? Yes
Persistent URL http://hdl.handle.net/10536/DRO/DU:30152083

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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.