Objective

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.

Methods

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 with glucose and insulin tolerance tests in models of diet-induced obesity.

Results

We report here 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.

Conclusion

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.

中文翻译：

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米色脂肪对于与肌生长抑制素缺失相关的代谢益处是可有可无的

客观的

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。肌肉生长抑制素无效小鼠的骨骼肌质量增加，并免受肥胖及其后遗症的影响。也有人建议删除肌生长抑制素会导致米色脂肪细胞、具有抗肥胖和抗糖尿病特性的产热脂肪细胞的激活。不知道米色脂肪激活是否有助于防止肌肉生长抑制素无效小鼠的肥胖。

方法

为了研究米色脂肪激活在与肌生长抑制素缺失相关的代谢益处中的作用，我们将肌生长抑制素缺失小鼠与脂肪细胞特异性 PRDM16 基因敲除小鼠杂交。我们在饮食诱导的肥胖模型中使用分子谱分析、整体三维组织成像、组织呼吸以及葡萄糖和胰岛素耐受性测试分析了这种新的小鼠模型。

结果

我们在此报告，在没有肌生长抑制素的情况下，激活米色脂肪需要 PRDM16。然而，我们在雄性和雌性小鼠中都表明，米色脂肪激活对于防止肥胖、葡萄糖耐受不良、胰岛素抵抗和肌肉生长抑制素缺失介导的肝脂肪变性是可有可无的。

结论

这些发现表明，增加肌肉质量可以补偿米色脂肪的失活，并提高将肌肉质量作为治疗方法的可能性，以抵消脂肪组织功能障碍对肥胖和代谢综合征的有害影响。