PMID:16182246

Citation	Zhao, B, Wall, RJ and Yang, J (2005) Transgenic expression of myostatin propeptide prevents diet-induced obesity and insulin resistance. Biochem. Biophys. Res. Commun. 337:248-55
Abstract	Obesity and insulin resistance cause serious consequences to human health. To study effects of skeletal muscle growth on obesity prevention, we focused on a key gene of skeletal muscle named myostatin, which plays an inhibitory role in muscle growth and development. We generated transgenic mice through muscle-specific expression of the cDNA sequence (5'-region 886 nucleotides) encoding for the propeptide of myostatin. The transgene effectively depressed myostatin function. Transgenic mice showed dramatic growth and muscle mass by 9 weeks of age. Here we reported that individual major muscles of transgenic mice were 45-115% heavier than those of wild-type mice, maintained normal blood glucose, insulin sensitivity, and fat mass after a 2-month regimen with a high-fat diet (45% kcal fat). In contrast, high-fat diet induced wild-type mice with 170-214% more fat mass than transgenic mice and developed impaired glucose tolerance and insulin resistance. Insulin signaling, measured by Akt phosphorylation, was significantly elevated by 144% in transgenic mice over wild-type mice fed a high-fat diet. Interestingly, high-fat diet significantly increased adiponectin secretion while blood insulin, resistin, and leptin levels remained normal in the transgenic mice. The results suggest that disruption of myostatin function by its propeptide favours dietary fat utilization for muscle growth and maintenance. An increased secretion of adiponectin may promote energy partition toward skeletal muscles, suggesting that a beneficial interaction between muscle and adipose tissue play a role in preventing obesity and insulin resistance.
Links	PubMed Online version:10.1016/j.bbrc.2005.09.044
Keywords	Adipose Tissue/metabolism; Adipose Tissue/pathology; Animals; Dietary Fats/administration & dosage; Gene Expression; Hormones/blood; Insulin Resistance; Mice; Mice, Transgenic; Muscle, Skeletal/metabolism; Muscle, Skeletal/pathology; Myostatin; Obesity/etiology; Obesity/pathology; Obesity/prevention & control; Peptides/genetics; Peptides/metabolism; Protein Precursors/genetics; Protein Precursors/metabolism; Transforming Growth Factor beta/antagonists & inhibitors; Transforming Growth Factor beta/genetics; Transforming Growth Factor beta/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:GDF8	involved_in	GO:0046627: negative regulation of insulin receptor signaling pathway	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:GDF8		GO:0046627: negative regulation of insulin receptor signaling pathway	ECO:0000315:		P		Responses of insulin action.. Section; Fig 3; muscle protein kinase Akt intermediate phosphorylation was measured due to is role in the insulin signaling pathway, transgenic mice showed greater levels [inhibition of myostatin] of phosphorylation	complete CACAO 6340

References

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