@article{09a8bcb3879d485ea5416133d9ccd9bf,
title = "Yap regulates skeletal muscle fatty acid oxidation and adiposity in metabolic disease",
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 {\textquoteleft}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.",
author = "Watt, {K. I.} and Henstridge, {D. C.} and M. Ziemann and Sim, {C. B.} and Montgomery, {M. K.} and D. Samocha-Bonet and Parker, {B. L.} and Dodd, {G. T.} and Bond, {S. T.} and Salmi, {T. M.} and Lee, {R. S.} and Thomson, {R. E.} and A. Hagg and Davey, {J. R.} and H. Qian and R. Koopman and A. El-Osta and Greenfield, {J. R.} and Watt, {M. J.} and Febbraio, {M. A.} and Drew, {B. G.} and Cox, {A. G.} and Porrello, {E. R.} and Harvey, {K. F.} and P. Gregorevic",
note = "Funding Information: We thank Stephanie Jansen and Prue O{\textquoteright}Hare, AMREP animal services, Melbourne for technical assistance. We acknowledge Dr Daniel Chan, Garvan Institute, Sydney who collected human muscle biopsies used in this study and express our gratitude to the subjects that participated in the studies that collected muscle biopsies. We acknowledge Metabolomics Australia for their contribution to this work. We also acknowledge the use of Illumina sequencing at the Australian Genome Research Facility and the Victorian Clinical Genetics Service (and the support they receive from the Commonwealth of Australia). Figure schematics were generated using BioRender (https://app.biorender. com/). This work was supported by a Project grant from the Australian National Health and Medical Research Council (NHMRC) (awarded to K.F.H. and P.G.) and a Diabetes Australia general grant (awarded to K.I.W.). P.G., A.E.O., M.J.W. and K.F.H. are supported by Senior Research Fellowships, M.A.F. by a Principal Research Fellowship and M.K.M. by a career development fellowship (all from the NHMRC). A.G.C. is supported by an Investigator grant from the NHMRC and a future fellowship from the Australian Research Council. B.G.D. is supported by a National Heart Foundation of Australia Future Leader Fellowship (101789). The University of Melbourne, Monash University, Deakin University, the Murdoch Children{\textquoteright}s Research Institute and the Baker Heart and Diabetes Institute are supported in part by the Operational Infrastructure Support Programme of the Victorian Government. Publisher Copyright: {\textcopyright} 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = dec,
doi = "10.1038/s41467-021-23240-7",
language = "English",
volume = "12",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}
