Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America ; Center for Metabolism and Obesity Research, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
PLoS One. 2014 Feb 20;9(2):e88535. doi: 10.1371/journal.pone.0088535. eCollection 2014.
CTRP2 is a secreted plasma protein of the C1q family that enhances glycogen deposition and fat oxidation in cultured myotubes. Its in vivo metabolic function, however, has not been established. We show here that acute and chronic metabolic perturbations induced by fasting or high-fat feeding up-regulated the mRNA expression of Ctrp2 in white adipose tissue without affecting its circulating plasma levels. We generated a transgenic mouse model with elevated circulating levels of CTRP2 to determine its metabolic function in vivo. When fed a low-fat diet, wild-type and CTRP2 transgenic mice exhibited no metabolic phenotypes. When challenged with a high-fat diet to induce obesity, wild-type and CTRP2 transgenic mice had similar weight gain, adiposity, food intake, metabolic rate, and energy expenditure. Fasting serum lipid and adipokine profiles were also similar between the two groups of mice. However, while glucose and insulin levels in the fasted state were comparable between wild-type and CTRP2 transgenic mice, insulin levels in the fed state were consistently lower in transgenic mice. Notably, CTRP2 transgenic mice had improved insulin tolerance and a greater capacity to handle acute lipid challenge relative to littermate controls. Our results highlight, for the first time, the in vivo role of CTRP2 in modulating whole-body metabolism.
CTRP2 是 C1q 家族的一种分泌性血浆蛋白，可增强培养的肌管中的糖原沉积和脂肪氧化。然而，其在体内的代谢功能尚未确定。我们在此表明，禁食或高脂肪喂养引起的急性和慢性代谢紊乱会上调白色脂肪组织中 Ctrp2 的 mRNA 表达，而不会影响其循环血浆水平。我们生成了一种具有升高的循环 CTRP2 水平的转基因小鼠模型，以确定其在体内的代谢功能。当喂食低脂饮食时，野生型和 CTRP2 转基因小鼠没有表现出代谢表型。当用高脂肪饮食挑战诱导肥胖时，野生型和 CTRP2 转基因小鼠的体重增加、肥胖、食物摄入、代谢率和能量消耗相似。两组小鼠的禁食血清脂质和脂肪因子谱也相似。然而，尽管野生型和 CTRP2 转基因小鼠在禁食状态下的血糖和胰岛素水平相当，但在进食状态下，转基因小鼠的胰岛素水平始终较低。值得注意的是，与同窝对照相比，CTRP2 转基因小鼠的胰岛素耐受性更好，并且能够更好地处理急性脂质挑战。我们的研究结果首次强调了 CTRP2 在调节全身代谢中的体内作用。
