Regulation of muscle metabolism by myostatin

肌肉生长抑制素对肌肉代谢的调节

• 批准号: 8553558
• 负责人: Alexandra Christine McPherron
• 金额: $ 24.67万
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8553558
• 关键词: Address; Cell Culture Techniques; Diabetes Mellitus; Diabetic mouse; Disease; Eating; Exercise; Fatty acid glycerol esters; Fiber; Gastrocnemius Muscle; Gene Expression; Genetic Models; Goals; Hyperglycemia; Hyperphagia; Knockout Mice; Lipodystrophy; Methods; Modeling; Molecular; Mus; Muscle; Muscle Development; Muscle Fibers; Obesity; Phenotype; Regulation; Role; Skeletal Muscle; Therapeutic; Transforming Growth Factor beta; Triglycerides; diabetic; enzyme activity; member; mouse model; muscle form; muscle metabolism; myostatin; prevent; treatment strategy

We have shown that, despite their increased glycolytic muscle fiber composition, myostatin deficient mice are able to perform endurance exercise without incurring muscle damage. Myostatin deficient mice are able to successfully adapt to endurance exercise by increasing oxidative enzyme activity. Myostatin deficient mice do, however, have a decrease in overall exercise capacity. We have also analyzed gene expression changes in gastrocnemius skeletal muscle with and without myostatin inhibition in a model of diabetes to determine the molecular mechanisms of myostatin regulation of muscle metabolism at the molecular level. We have shown that myostatin inhibition specifically in muscle in a mouse model of lipodystrophy prevents the accumulation of triglycerides in muscle, the development of hyperglycemia, and hyperphagia. These results suggest that increased muscle may not only help prevent diabetes, but may also regulate food intake.

我们已经证明，尽管糖酵解肌纤维成分增加，但肌生长抑制素缺乏的小鼠能够进行耐力运动而不会造成肌肉损伤。肌肉生长抑制素缺乏的小鼠能够通过增加氧化酶活性成功地适应耐力运动。然而，肌肉生长抑制素缺乏的小鼠的整体运动能力确实有所下降。我们还分析了糖尿病模型中有和没有肌生长抑制素抑制的腓肠肌骨骼肌的基因表达变化，以确定肌生长抑制素在分子水平上调节肌肉代谢的分子机制。我们已经证明，在脂肪营养不良小鼠模型的肌肉中，特别抑制肌肉生长抑制素可以防止肌肉中甘油三酯的积累、高血糖和食欲亢进的发生。这些结果表明，增加肌肉不仅有助于预防糖尿病，还可以调节食物摄入量。