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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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Mean (+SEM) muscle and intra-abdominal adipose tissue mass.Myostatin-deficient (gray bars) and control mice (white bars) were fed a normal low-fat diet (13% of energy from fat) or were fed a high-fat diet (60% of energy from fat) for the final 22 weeks of the experiment. Each bar represents the mean and SEM of 12–15 mice. *P<0.001 versus mice with normal myostatin levels.
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pone-0017090-g002: Mean (+SEM) muscle and intra-abdominal adipose tissue mass.Myostatin-deficient (gray bars) and control mice (white bars) were fed a normal low-fat diet (13% of energy from fat) or were fed a high-fat diet (60% of energy from fat) for the final 22 weeks of the experiment. Each bar represents the mean and SEM of 12–15 mice. *P<0.001 versus mice with normal myostatin levels.

Mentions: At the end of the study, the mass of fat within the abdominal cavity was more than 5-fold greater in the high-fat groups than in low-fat groups (Figure 2). Myostatin depletion did not significantly affect the mass of epididymal or retroperitoneal fat at the end of the study in either the low-fat or the high-fat groups. In mice with normal myostatin genes, the high-fat diet increased hepatic mass by 30% (Table 1). In myostatin-deficient mice, the high-fat diet did not consistently increase hepatic mass (mean+5%, P = 0.4). Myocardial mass was increased by the high-fat diet, 14% in control mice and 10% in myostatin-deficient mice. Kidney mass was not significantly affected by the high-fat diet in either normal or myostatin-deficient mice (P>0.1, Table 1). We did not weigh the gastrointestinal tract or other organs, but by visual inspection we did not notice any major effects of the high-fat diet or myostatin depletion on the size of internal organs. Skeletal muscle mass (gastrocnemius, quadriceps, and triceps muscles) was about 30% greater than normal in myostatin-deficient mice, as expected, regardless of dietary condition (Table 1, Figure 2).


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)

Mean (+SEM) muscle and intra-abdominal adipose tissue mass.Myostatin-deficient (gray bars) and control mice (white bars) were fed a normal low-fat diet (13% of energy from fat) or were fed a high-fat diet (60% of energy from fat) for the final 22 weeks of the experiment. Each bar represents the mean and SEM of 12–15 mice. *P<0.001 versus mice with normal myostatin levels.
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Related In: Results  -  Collection

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

pone-0017090-g002: Mean (+SEM) muscle and intra-abdominal adipose tissue mass.Myostatin-deficient (gray bars) and control mice (white bars) were fed a normal low-fat diet (13% of energy from fat) or were fed a high-fat diet (60% of energy from fat) for the final 22 weeks of the experiment. Each bar represents the mean and SEM of 12–15 mice. *P<0.001 versus mice with normal myostatin levels.
Mentions: At the end of the study, the mass of fat within the abdominal cavity was more than 5-fold greater in the high-fat groups than in low-fat groups (Figure 2). Myostatin depletion did not significantly affect the mass of epididymal or retroperitoneal fat at the end of the study in either the low-fat or the high-fat groups. In mice with normal myostatin genes, the high-fat diet increased hepatic mass by 30% (Table 1). In myostatin-deficient mice, the high-fat diet did not consistently increase hepatic mass (mean+5%, P = 0.4). Myocardial mass was increased by the high-fat diet, 14% in control mice and 10% in myostatin-deficient mice. Kidney mass was not significantly affected by the high-fat diet in either normal or myostatin-deficient mice (P>0.1, Table 1). We did not weigh the gastrointestinal tract or other organs, but by visual inspection we did not notice any major effects of the high-fat diet or myostatin depletion on the size of internal organs. Skeletal muscle mass (gastrocnemius, quadriceps, and triceps muscles) was about 30% greater than normal in myostatin-deficient mice, as expected, regardless of dietary condition (Table 1, Figure 2).

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