Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
FASEB J. 2019 Jul;33(7):8666-8687. doi: 10.1096/fj.201900520R. Epub 2019 Apr 19.
We recently described myonectin (also known as erythroferrone) as a novel skeletal muscle-derived myokine with metabolic functions. Here, we use a genetic mouse model to determine myonectin's requirement for metabolic homeostasis. Female myonectin-deficient mice had larger gonadal fat pads and developed mild insulin resistance when fed a high-fat diet (HFD) and had reduced food intake during refeeding after an unfed period but were otherwise indistinguishable from wild-type littermates. Male mice lacking myonectin, however, had reduced physical activity when fed and in the postprandial state but not during the unfed period. When stressed with an HFD, myonectin-knockout male mice had significantly elevated VLDL-triglyceride (TG) and strikingly impaired lipid clearance from circulation following an oral lipid load. Fat distribution between adipose and liver was also altered in myonectin-deficient male mice fed an HFD. Greater fat storage resulted in significantly enlarged adipocytes and was associated with increased postprandial lipoprotein lipase activity in adipose tissue. Parallel to this was a striking reduction in liver steatosis due to significantly reduced TG accumulation. Liver metabolite profiling revealed additional significant changes in bile acids and 1-carbon metabolism pathways. Combined, our data affirm the physiologic importance of myonectin in regulating local and systemic lipid metabolism.-Little, H. C., Rodriguez, S., Lei, X., Tan, S. Y., Stewart, A. N., Sahagun, A., Sarver, D. C., Wong, G. W. Myonectin deletion promotes adipose fat storage and reduces liver steatosis.
我们最近将肌联蛋白（也称为红细胞生成素）描述为一种具有代谢功能的新型骨骼肌衍生肌因子。在这里，我们使用遗传小鼠模型来确定肌联蛋白在代谢稳态中的需求。雌性肌联蛋白缺陷型小鼠的生殖腺脂肪垫较大，在高脂饮食（HFD）喂养时表现出轻度胰岛素抵抗，在禁食期后重新进食时食物摄入量减少，但与野生型同窝仔鼠没有区别。然而，缺乏肌联蛋白的雄性小鼠在喂食和餐后状态下的体力活动减少，但在禁食期间没有减少。当用 HFD 施加压力时，肌联蛋白敲除雄性小鼠的 VLDL-甘油三酯（TG）显著升高，并且在口服脂质负荷后脂质从循环中清除的能力明显受损。在喂食 HFD 的肌联蛋白缺陷型雄性小鼠中，脂肪在脂肪组织和肝脏之间的分布也发生了改变。更多的脂肪储存导致脂肪细胞显著增大，并与脂肪组织中餐后脂蛋白脂肪酶活性增加相关。与此平行的是，由于 TG 积累显著减少，肝脂肪变性明显减少。肝脏代谢产物谱分析显示胆汁酸和 1 碳代谢途径也有显著变化。综合来看，我们的数据证实了肌联蛋白在调节局部和全身脂质代谢中的生理重要性。
