Soluble activin receptor type IIB treatment does not cause fat loss in mice with diet-induced obesity.
The growth factor myostatin (MSTN) negatively regulates skeletal muscle mass. Mstn gene deletion in mice causes increased muscle mass, reduced adiposity and resistance to genetic or diet-induced obesity (DIO). Pharmacologic MSTN inhibition in mice also causes increased muscle mass and resistance to DIO. To test whether MSTN inhibition causes weight loss in mice that are already obese, we inhibited MSTN in mice fed a high-fat diet (HFD). Mice were fed a diet containing 60% kcal from fat for 12 weeks followed by treatment with a soluble MSTN receptor derived from the activin receptor type IIB extracellular domain. During the next 12 weeks of soluble receptor treatment and HFD feeding, lean mass increased without a loss of adipose mass. Glucose metabolism was also similar between groups. Our results suggest that MSTN inhibition may be ineffective at inducing weight loss in obese patients.
Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA. mcpherrona@niddk.nih.gov
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Portas
D030301:Activin Receptors, Type II / Q000494:pharmacology*; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D059305:Diet, High-Fat; D002149:Energy Intake; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D055435:Myostatin / Q000037:antagonists & inhibitors* / Q000378:metabolism* / Q000494:pharmacology; D009765:Obesity / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism
D055435:Myostatin; D030301:Activin Receptors, Type II; C425584:activin receptor type II-B