Laboratory of Molecular Metabolism, The Rockefeller University, 1230 York Avenue, New York City, NY 10065, USA.
Laboratory of Molecular Metabolism, The Rockefeller University, 1230 York Avenue, New York City, NY 10065, USA.
Mol Metab. 2021 Jan;43:101120. doi: 10.1016/j.molmet.2020.101120. Epub 2020 Nov 18.
Increasing muscle mass and activating beige fat both have great potential for ameliorating obesity and its comorbidities. Myostatin null mice have increased skeletal muscle mass and are protected from obesity and its sequelae. Deletion of myostatin has also been suggested to result in the activation of beige adipocytes, thermogenic fat cells with anti-obesity and anti-diabetes properties. It is not known whether beige fat activation contributes to the protection from obesity in myostatin null mice.
To investigate the role of beige fat activation in the metabolic benefits associated with myostatin deletion, we crossed myostatin null mice to adipocyte-specific PRDM16 knockout mice. We analyzed this new mouse model using molecular profiling, whole mount three-dimensional tissue imaging, tissue respiration, and glucose and insulin tolerance tests in models of diet-induced obesity.
Here, we report that PRDM16 is required for the activation of beige fat in the absence of myostatin. However, we show in both male and female mice that beige fat activation is dispensable for the protection from obesity, glucose intolerance, insulin resistance, and hepatic steatosis mediated by myostatin deletion.
These findings demonstrate that increasing muscle mass can compensate for the inactivation of beige fat and raise the possibility of targeting muscle mass as a therapeutic approach to offset the deleterious effects of adipose tissue dysfunction in obesity and metabolic syndrome.
增加肌肉质量和激活米色脂肪都具有改善肥胖及其合并症的巨大潜力。肌肉生长抑制素缺失的小鼠具有增加的骨骼肌质量，并免受肥胖及其后遗症的影响。肌肉生长抑制素的缺失也被认为导致米色脂肪细胞的激活，米色脂肪细胞是具有抗肥胖和抗糖尿病特性的产热脂肪细胞。目前尚不清楚米色脂肪细胞的激活是否有助于肌肉生长抑制素缺失的小鼠预防肥胖。
为了研究米色脂肪细胞激活在与肌肉生长抑制素缺失相关的代谢益处中的作用，我们将肌肉生长抑制素缺失的小鼠与脂肪细胞特异性 PRDM16 缺失的小鼠进行了杂交。我们使用分子谱分析、整体三维组织成像、组织呼吸以及葡萄糖和胰岛素耐量试验，在饮食诱导肥胖的模型中分析了这种新的小鼠模型。
在这里，我们报告 PRDM16 在肌肉生长抑制素缺失时米色脂肪细胞的激活中是必需的。然而，我们在雄性和雌性小鼠中均表明，米色脂肪细胞的激活对于肌肉生长抑制素缺失介导的肥胖、葡萄糖不耐受、胰岛素抵抗和肝脂肪变性的保护作用是可有可无的。
这些发现表明，增加肌肉质量可以弥补米色脂肪细胞失活的影响，并提出了将肌肉质量作为一种治疗方法来抵消肥胖和代谢综合征中脂肪组织功能障碍的有害影响的可能性。
