Activating HSP72 in rodent skeletal muscle increases mitochondrial number and oxidative capacity and decreases insulin resistance

DC Henstridge; CR Bruce; BG Drew; K Tory; A Kolonics; E Estevez; J Chung; N Watson; T Gardner; RS Lee-Young; T Connor; MJ Watt; K Carpenter; M Hargreaves; SL McGee; AL Hevener; MA Febbraio

Journal article

Activating HSP72 in rodent skeletal muscle increases mitochondrial number and oxidative capacity and decreases insulin resistance

DC Henstridge, CR Bruce, BG Drew, K Tory, A Kolonics, E Estevez, J Chung, N Watson, T Gardner, RS Lee-Young, T Connor, MJ Watt, K Carpenter, M Hargreaves, SL McGee, AL Hevener, MA Febbraio

Diabetes | AMER DIABETES ASSOC | Published : 2014

DOI: 10.2337/db13-0967

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Abstract

Induction of heat shock protein (HSP)72 protects against obesity-induced insulin resistance, but the underlying mechanisms are unknown. Here, we show that HSP72 plays a pivotal role in increasing skeletal muscle mitochondrial number and oxidative metabolism. Mice overexpressing HSP72 in skeletal muscle (HSP72Tg) and control wild-type (WT) mice were fed either a chow or high-fat diet (HFD). Despite a similar energy intake when HSP72Tg mice were compared with WT mice, the HFD increased body weight, intramuscular lipid accumulation (triacylglycerol and diacylglycerol but not ceramide), and severe glucose intolerance in WT mice alone. Whole-body VO2, fatty acid oxidation, and endurance running c..

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University of Melbourne Researchers

Matt Watt Author

Mark Hargreaves Author

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Awarded by National Institutes of Health

Funding Acknowledgements

This study was supported by grants from the National Health and Medical Research Council of Australia (National Health and Medical Research Council [NHMRC] Project grant 1004441 to M.A.F., C.R.B., M.H., and S.L.M.) and the Victorian Government Operational Infrastructure Support Program. C.R.B. and S.L.M. are supported by Career Development Awards of the NHMRC. B.G.D. is supported by an Overseas Postdoctoral Fellowship of the NHMRC and a University of California, Los Angeles (UCLA), Jonsson Cancer Centre Foundation Fellowship. M.J.W. is a Senior Research Fellow and M.A.F. a Senior Principal Research Fellow of the NHMRC. D.C.H. is supported by a National Heart Foundation Biomedical Postdoctoral Fellowship and an Australian Diabetes Society Skip Martin Fellowship. R.S.L.-Y. is supported by NHMRC Project grant 1004212. A.L.H. is supported by the UCLA Department of Medicine and the National Institutes of Health (R01DK78760, R01DK089109, and P30DK063491).