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Skeletal muscle‐specific overexpression of heat shock protein 72 improves skeletal muscle insulin‐stimulated glucose uptake but does not alter whole body metabolism
Author(s) -
Marshall Jessica P. S.,
Estevez Emma,
Kammoun Helene L.,
King Emily J.,
Bruce Clinton R.,
Drew Brian G.,
Qian Hongwei,
Iliades Peter,
Gregorevic Paul,
Febbraio Mark A.,
Henstridge Darren C.
Publication year - 2018
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.13319
Subject(s) - skeletal muscle , medicine , insulin resistance , endocrinology , hindlimb , insulin , heat shock protein , glucose uptake , carbohydrate metabolism , biology , biochemistry , gene
Aims The induction of heat shock protein 72 (Hsp72) via heating, genetic manipulation or pharmacological activation is metabolically protective in the setting of obesity‐induced insulin resistance across mammalian species. In this study, we set out to determine whether the overexpression of Hsp72, specifically in skeletal muscle, can protect against high‐fat diet (HFD)‐induced obesity and insulin resistance. Materials and methods An Adeno‐Associated Viral vector (AAV), designed to overexpress Hsp72 in skeletal muscle only, was used to study the effects of increasing Hsp72 levels on various metabolic parameters. Two studies were conducted, the first with direct intramuscular (IM) injection of the AAV:Hsp72 into the tibialis anterior hind‐limb muscle and the second with a systemic injection to enable body‐wide skeletal muscle transduction. Results IM injection of the AAV:Hsp72 significantly improved skeletal muscle insulin‐stimulated glucose clearance in treated hind‐limb muscles, as compared with untreated muscles of the contralateral leg when mice were fed an HFD. Despite this finding, systemic administration of AAV:Hsp72 did not improve body composition parameters such as body weight, fat mass or percentage body fat, nor did it lead to an improvement in fasting glucose levels or glucose tolerance. Furthermore, no differences were observed for other metabolic parameters such as whole‐body oxygen consumption, energy expenditure or physical activity levels. Conclusions At the levels of Hsp72 over‐expression reported herein, skeletal muscle‐specific Hsp72 overexpression via IM injection has the capacity to increase insulin‐stimulated glucose clearance in this muscle. However, upon systemic injection, which results in lower muscle Hsp72 overexpression, no beneficial effects on whole‐body metabolism are observed.