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Effect of myostatin depletion on weight gain, hyperglycemia, and hepatic steatosis during five months of high-fat feeding in mice.

Burgess K, Xu T, Brown R, Han B, Welle S - PLoS ONE (2011)

Bottom Line: We therefore examined how postdevelopmental myostatin knockout influenced effects of high-fat feeding.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.We conclude that blocking myostatin signaling after maturity can attenuate some of the adverse effects of a high-fat diet.

View Article: PubMed Central - PubMed

Affiliation: Endocrinology and Metabolism Division, Department of Medicine, University of Rochester, Rochester, New York, United States of America.

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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Hepatic steatosis scores and representative micrographs of liver sections.Distribution of steatosis scores (A) is based on examination of 12 mice with normal myostatin expression and 13 myostatin-deficient mice, all of which received the high-fat diet. Mice fed a low-fat diet did not have hepatic fat accumulation (B, Osmium H&E×250). Mice with normal myostatin expression had significant hepatic steatosis after 5 months of high-fat feeding (C×250; D×500). Larger lipid droplets often lift off the tissue leaving the clear spaces seen in the micrographs. Less fat accumulation was evident in livers of myostatin-deficient mice fed a high-fat diet for 5 months (E×250; F×500).
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pone-0017090-g005: Hepatic steatosis scores and representative micrographs of liver sections.Distribution of steatosis scores (A) is based on examination of 12 mice with normal myostatin expression and 13 myostatin-deficient mice, all of which received the high-fat diet. Mice fed a low-fat diet did not have hepatic fat accumulation (B, Osmium H&E×250). Mice with normal myostatin expression had significant hepatic steatosis after 5 months of high-fat feeding (C×250; D×500). Larger lipid droplets often lift off the tissue leaving the clear spaces seen in the micrographs. Less fat accumulation was evident in livers of myostatin-deficient mice fed a high-fat diet for 5 months (E×250; F×500).

Mentions: The high-fat diet induced an increase of ∼4-fold in the amount of fat in triceps muscles in mice with normal myostatin levels (Figure 4). In contrast, the high-fat diet increased muscle fat content only 60% in myostatin-deficient mice. The method used to assess muscle fat content did not differentiate between fat within the muscle fibers and fat that accumulated in adipocytes between muscle fibers. Fat deposition in the liver also was attenuated in myostatin-deficient mice (Figure 5). All 12 livers from control mice fed the high-fat diet received the highest steatosis score, whereas only 5 of 13 livers from myostatin-deficient mice received the highest score. The difference between control and myostatin-deficient mice in the distribution of steatosis scores was significant by Fisher's exact probability test (P<0.01).


Effect of myostatin depletion on weight gain, hyperglycemia, and hepatic steatosis during five months of high-fat feeding in mice.

Burgess K, Xu T, Brown R, Han B, Welle S - PLoS ONE (2011)

Hepatic steatosis scores and representative micrographs of liver sections.Distribution of steatosis scores (A) is based on examination of 12 mice with normal myostatin expression and 13 myostatin-deficient mice, all of which received the high-fat diet. Mice fed a low-fat diet did not have hepatic fat accumulation (B, Osmium H&E×250). Mice with normal myostatin expression had significant hepatic steatosis after 5 months of high-fat feeding (C×250; D×500). Larger lipid droplets often lift off the tissue leaving the clear spaces seen in the micrographs. Less fat accumulation was evident in livers of myostatin-deficient mice fed a high-fat diet for 5 months (E×250; F×500).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3044753&req=5

pone-0017090-g005: Hepatic steatosis scores and representative micrographs of liver sections.Distribution of steatosis scores (A) is based on examination of 12 mice with normal myostatin expression and 13 myostatin-deficient mice, all of which received the high-fat diet. Mice fed a low-fat diet did not have hepatic fat accumulation (B, Osmium H&E×250). Mice with normal myostatin expression had significant hepatic steatosis after 5 months of high-fat feeding (C×250; D×500). Larger lipid droplets often lift off the tissue leaving the clear spaces seen in the micrographs. Less fat accumulation was evident in livers of myostatin-deficient mice fed a high-fat diet for 5 months (E×250; F×500).
Mentions: The high-fat diet induced an increase of ∼4-fold in the amount of fat in triceps muscles in mice with normal myostatin levels (Figure 4). In contrast, the high-fat diet increased muscle fat content only 60% in myostatin-deficient mice. The method used to assess muscle fat content did not differentiate between fat within the muscle fibers and fat that accumulated in adipocytes between muscle fibers. Fat deposition in the liver also was attenuated in myostatin-deficient mice (Figure 5). All 12 livers from control mice fed the high-fat diet received the highest steatosis score, whereas only 5 of 13 livers from myostatin-deficient mice received the highest score. The difference between control and myostatin-deficient mice in the distribution of steatosis scores was significant by Fisher's exact probability test (P<0.01).

Bottom Line: We therefore examined how postdevelopmental myostatin knockout influenced effects of high-fat feeding.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.We conclude that blocking myostatin signaling after maturity can attenuate some of the adverse effects of a high-fat diet.

View Article: PubMed Central - PubMed

Affiliation: Endocrinology and Metabolism Division, Department of Medicine, University of Rochester, Rochester, New York, United States of America.

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.

Show MeSH
Related in: MedlinePlus