The Vicious Cycle of Myostatin Signaling in Sarcopenic Obesity: Myostatin Role in Skeletal Muscle Growth, Insulin Signaling and Implications for Clinical Trials.
The Vicious Cycle of Myostatin Signaling in Sarcopenic Obesity: Myostatin Role in Skeletal Muscle Growth, Insulin Signaling and Implications for Clinical Trials.
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DOI：
10.14283/jfa.2017.33
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Clark BC
中科院分区：
文献类型：
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作者：
Consitt LA;Clark BC
与年龄相关的骨骼肌损失（肌肉减少症）是一个主要的健康问题，因为它与身体残疾，代谢障碍和死亡率增加有关。肌肉减少症与肥胖的共存，称为“肌肉减少性肥胖”，有助于骨骼肌胰岛素抵抗和2型糖尿病的发展，2型糖尿病是一种随年龄增长而流行的疾病。尽管有这些知识，但导致肌肉减少性肥胖的机制仍然知之甚少，阻碍了靶向治疗的发展。本文将讨论肌肉减少性肥胖的临床和生理后果，并提出肌生长抑制素作为一个潜在的候选人，有助于这种情况。一个特别的重点将放在检查肌肉生长抑制素信号在损害骨骼肌生长和胰岛素信号的作用。此外，肌肉生长抑制素在调节肌肉与脂肪的相互作用，进一步加剧老年人代谢功能障碍方面的作用也将得到强调。最后，我们讨论了这些知识如何影响肌肉生长抑制素抑制剂临床试验的设计。
The age-related loss of skeletal muscle (sarcopenia) is a major health concern as it is associated with physical disability, metabolic impairments, and increased mortality. The coexistence of sarcopenia with obesity, termed ‘sarcopenic obesity’, contributes to skeletal muscle insulin resistance and the development of type 2 diabetes, a disease prevalent with advancing age. Despite this knowledge, the mechanisms contributing to sarcopenic obesity remain poorly understood, preventing the development of targeted therapeutics. This article will discuss the clinical and physiological consequences of sarcopenic obesity and propose myostatin as a potential candidate contributing to this condition. A special emphasis will be placed on examining the role of myostatin signaling in impairing both skeletal muscle growth and insulin signaling. In addition, the role of myostatin in regulating muscle-to fat cross talk, further exacerbating metabolic dysfunction in the elderly, will be highlighted. Lastly, we discuss how this knowledge has implications for the design of myostatin-inhibitor clinical trials.