Article

Effect of Myostatin Depletion on Weight Gain, Hyperglycemia, and Hepatic Steatosis during Five Months of High-Fat Feeding in Mice

University of California, Los Angeles, and Cedars-Sinai Medical Center, United States of America
PLoS ONE (Impact Factor: 3.23). 02/2011; 6(2):e17090. DOI: 10.1371/journal.pone.0017090
Source: PubMed

ABSTRACT The marked hypermuscularity in mice with constitutive myostatin deficiency reduces fat accumulation and hyperglycemia induced by high-fat feeding, but it is unclear whether the smaller increase in muscle mass caused by postdevelopmental loss of myostatin activity has beneficial metabolic effects during high-fat feeding. We therefore examined how postdevelopmental myostatin knockout influenced effects of high-fat feeding. Male mice with ubiquitous expression of tamoxifen-inducible Cre recombinase were fed tamoxifen for 2 weeks at 4 months of age. This depleted myostatin in mice with floxed myostatin genes, but not in control mice with normal myostatin genes. Some mice were fed a high-fat diet (60% of energy) for 22 weeks, starting 2 weeks after cessation of tamoxifen feeding. Myostatin depletion increased skeletal muscle mass ∼30%. Hypermuscular mice had ∼50% less weight gain than control mice over the first 8 weeks of high-fat feeding. During the subsequent 3 months of high-fat feeding, additional weight gain was similar in control and myostatin-deficient mice. After 5 months of high-fat feeding, the mass of epididymal and retroperitoneal fat pads was similar in control and myostatin-deficient mice even though myostatin depletion reduced the weight gain attributable to the high-fat diet (mean weight with high-fat diet minus mean weight with low-fat diet: 19.9 g in control mice, 14.1 g in myostatin-deficient mice). Myostatin depletion did not alter fasting blood glucose levels after 3 or 5 months of high-fat feeding, but reduced glucose levels measured 90 min after intraperitoneal glucose injection. Myostatin depletion also attenuated hepatic steatosis and accumulation of fat in muscle tissue. We conclude that blocking myostatin signaling after maturity can attenuate some of the adverse effects of a high-fat diet.

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Available from: Tianshun Xu, Jul 25, 2014
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    • "Myostatin knockout mice have a dramatic increase in muscle mass, a reduction in fat mass and a resistance to obesity caused by diet and genetic mutation (McPherron and Lee, 2002; Guo et al., 2009). Because muscle is a significant glucose consumer, it is not surprising that constitutive myostatin depletion by conditional genetic mutation (Wilkes et al., 2009; Burgess et al., 2011) and application of a myostatin receptor blocker (Akpan et al., 2009) can reduce weight gain and improve hyperglycemia, IR and hepatic steatosis caused by a high-fat diet in mice. Follistatin is known to be the most potent antagonist of myostatin (Lee and McPherron, 2001; Haidet et al., 2008) and has been reported as a candidate gene for women with PCOS (Urbanek et al., 1999). "
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