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


Henstridge, DC and Bruce, CR and Drew, BG and Tory, K and Kolonics, A and Estevez, E and Chung, J and Watson, N and Gardner, T and Lee-Young, RS and Connor, T and Watt, MJ and Carpenter, K and Hargreaves, M and McGee, SL and Hevener, AL and Febbraio, MA, Activating HSP72 in rodent skeletal muscle increases mitochondrial number and oxidative capacity and decreases insulin resistance, Diabetes, 63, (6) pp. 1881-1894. ISSN 0012-1797 (2014) [Refereed Article]


Copyright Statement

Copyright 2014 by the American Diabetes Association. Licensed under Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported (CC BY-NC-ND 3.0)

DOI: doi:10.2337/db13-0967


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 capacity were markedly increased in HSP72Tg mice. Moreover, HSP72Tg mice exhibited an increase in mitochondrial number. In addition, the HSP72 coinducer BGP-15, currently in human clinical trials for type 2 diabetes, also increased mitochondrial number and insulin sensitivity in a rat model of type 2 diabetes. Together, these data identify a novel role for activation of HSP72 in skeletal muscle. Thus, the increased oxidative metabolism associated with activation of HSP72 has potential clinical implications not only for type 2 diabetes but also for other disorders where mitochondrial function is compromised.

Item Details

Item Type:Refereed Article
Keywords:ceramide, diacylglycerol, fatty acid transporter, glucose, heat shock protein 72, insulin, o (2 hydroxy 3 piperidinopropyl) nicotinic amidoxime, sirtuin 1, triacylglycerol, aerobic metabolism, animal experiment, animal model, animal tissue, article
Research Division:Biological Sciences
Research Group:Biochemistry and cell biology
Research Field:Cell metabolism
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Henstridge, DC (Dr Darren Henstridge)
ID Code:133349
Year Published:2014
Web of Science® Times Cited:127
Deposited By:Health Sciences
Deposited On:2019-06-24
Last Modified:2019-07-22
Downloads:13 View Download Statistics

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