Please use this identifier to cite or link to this item: http://hdl.handle.net/1893/22898
Appears in Collections:Faculty of Health Sciences and Sport Journal Articles
Peer Review Status: Refereed
Title: High-fat diet-induced impairment of skeletal muscle insulin sensitivity is not prevented by SIRT1 overexpression
Authors: White, Amanda T
Philp, Andrew
Fridolfsson, Heidi N
Schilling, Jan M
Murphy, Anne N
Hamilton, David Lee
McCurdy, Carrie E
Patel, Hemal H
Schenk, Simon
Contact Email: d.l.hamilton@stir.ac.uk
Issue Date: 1-Nov-2014
Publisher: American Physiological Society
Citation: White AT, Philp A, Fridolfsson HN, Schilling JM, Murphy AN, Hamilton DL, McCurdy CE, Patel HH & Schenk S (2014) High-fat diet-induced impairment of skeletal muscle insulin sensitivity is not prevented by SIRT1 overexpression, American Journal of Physiology - Endocrinology and Metabolism, 307 (9), pp. E764-E772.
Abstract: Skeletal muscle sirtuin 1 (SIRT1) expression is reduced under insulin-resistant conditions, such as those resulting from high-fat diet (HFD) feeding and obesity. Herein, we investigated whether constitutive activation of SIRT1 in skeletal muscle prevents HFD-induced muscle insulin resistance. To address this, mice with muscle-specific overexpression of SIRT1 (mOX) and wild-type (WT) littermates were fed a control diet (10% calories from fat) or HFD (60% of calories from fat) for 12 wk. Magnetic resonance imaging and indirect calorimetry were used to measure body composition and energy expenditure, respectively. Whole body glucose metabolism was assessed by oral glucose tolerance test, and insulin-stimulated glucose uptake was measured at a physiological insulin concentration in isolated soleus and extensor digitorum longus muscles. Although SIRT1 was significantly overexpressed in muscle of mOX vs. WT mice, body weight and percent body fat were similarly increased by HFD for both genotypes, and energy expenditure was unaffected by diet or genotype. Importantly, impairments in glucose tolerance and insulin-mediated activation of glucose uptake in skeletal muscle that occurred with HFD feeding were not prevented in mOX mice. In contrast, mOX mice showed enhanced postischemic cardiac functional recovery compared with WT mice, confirming the physiological functionality of the SIRT1 transgene in this mouse model. Together, these results demonstrate that activation of SIRT1 in skeletal muscle alone does not prevent HFD-induced glucose intolerance, weight gain, or insulin resistance.
Type: Journal Article
URI: http://hdl.handle.net/1893/22898
DOI Link: http://dx.doi.org/10.1152/ajpendo.00001.2014
Rights: The publisher does not allow this work to be made publicly available in this Repository. Please use the Request a Copy feature at the foot of the Repository record to request a copy directly from the author. You can only request a copy if you wish to use this work for your own research or private study.
Affiliation: University of California, San Diego
University of Birmingham
University of California, San Diego
University of California, San Diego
University of California, San Diego
Sport
University of Oregon
University of California, San Diego
University of California, San Diego

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