PMID:21390326

Citation	Burgess, K, Xu, T, Brown, R, Han, B and Welle, S (2011) Effect of myostatin depletion on weight gain, hyperglycemia, and hepatic steatosis during five months of high-fat feeding in mice. PLoS ONE 6:e17090
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.
Links	PubMed PMC3044753 Online version:10.1371/journal.pone.0017090
Keywords	Animals; Blood Glucose/analysis; Blood Glucose/drug effects; Blood Glucose/metabolism; Diet, Atherogenic; Dietary Fats/adverse effects; Fatty Liver/blood; Fatty Liver/complications; Fatty Liver/etiology; Fatty Liver/genetics; Glucose/administration & dosage; Glucose/pharmacology; Hyperglycemia/blood; Hyperglycemia/chemically induced; Hyperglycemia/complications; Hyperglycemia/genetics; Injections, Intraperitoneal; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Myostatin/genetics; Myostatin/metabolism; Myostatin/physiology; Time Factors; Weight Gain/drug effects; Weight Gain/genetics; Weight Gain/physiology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:GDF8	involved_in	GO:0048632: negative regulation of skeletal muscle tissue growth	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:GDF8		GO:0048632: negative regulation of skeletal muscle tissue growth	ECO:0000315:		P		Table 1 and Figure 2 show the Gastrocnemius, Quadriceps, and Triceps muscles all were significantly larger in weight(g) in myostatin deficient mice compared to normal myostatin mice.	complete CACAO 3684
MOUSE:GDF8		GO:0019217: regulation of fatty acid metabolic process	ECO:0000315:		P		Figure 4 shows mg fatty acids per g of muscle tissue is significantly less in myostatin depleted mice fed a high-fat diet.	complete CACAO 3741
MOUSE:GDF8		GO:0043610: regulation of carbohydrate utilization	ECO:0000315:		P		Figure 3 shows blood glucose concentration is significantly lower in myostatin depleted mice fed a high-fat diet for 5 months, 90 min after ip glucose injection.	complete CACAO 3743
MOUSE:GDF8		GO:0019216:	ECO:0000315:				Figure 5 shows that myostatin depleted mice have a significantly lower incidence and severity of hepatic statosis when fed a high-fat diet for 5 months.	complete CACAO 3746

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