Cardiotrophin-1 Is a Key Regulator of Glucose and Lipid Metabolism
Cardiotrophin-1 Is a Key Regulator of Glucose and Lipid Metabolism
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DOI：
10.1016/j.cmet.2011.05.013
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发表时间：
2011-08-03
期刊：
影响因子：
29
通讯作者：
Bustos, Matilde
中科院分区：
文献类型：
--
作者：
Moreno-Aliaga, Maria J.;Perez-Echarri, Nerea;Bustos, Matilde
心促因子-1 （CT-1）是gp130细胞因子家族的一员。我们观察到，尽管减少卡路里摄入，ct-1（-/-）小鼠仍会出现成熟型肥胖、胰岛素抵抗和高胆固醇血症。能量消耗的减少在肥胖发生之前和伴随发生。急性治疗时，rCT-1以不依赖胰岛素的方式降低血糖，并增加胰岛素刺激的肌肉AKT磷酸化。这些变化与脂肪酸氧化刺激有关，而AMPK α 2（-/-）小鼠没有这种作用。慢性rCT-1治疗减少了食物摄入，增加了能量消耗，并诱导了白色脂肪组织重塑，其特征是与脂肪分解、脂肪酸氧化、线粒体生物发生和棕色脂肪表型基因相关的基因上调。此外，rCT-1降低了ob/ob和高脂肪喂养的肥胖小鼠的体重并纠正了胰岛素抵抗。我们得出结论，CT-1是脂肪和葡萄糖代谢的主要调节因子，在治疗肥胖和胰岛素抵抗方面具有潜在的应用前景。
Cardiotrophin-1 (CT-1) is a member of the gp130 family of cytokines. We observed that ct-1(-/-) mice develop mature-onset obesity, insulin resistance, and hypercholesterolemia despite reduced calorie intake. Decreased energy expenditure preceded and accompanied the development of obesity. Acute treatment with rCT-1 decreased blood glucose in an insulin-independent manner and increased insulin-stimulated AKT phosphorylation in muscle. These changes were associated with stimulation of fatty acid oxidation, an effect that was absent in AMPK alpha 2(-/-) mice. Chronic rCT-1 treatment reduced food intake, enhanced energy expenditure, and induced white adipose tissue remodeling characterized by upregulation of genes implicated in the control of lipolysis, fatty acid oxidation, and mitochondrial biogenesis and genes typifying brown fat phenotype. Moreover, rCT-1 reduced body weight and corrected insulin resistance in ob/ob and in high-fat-fed obese mice. We conclude that CT-1 is a master regulator of fat and glucose metabolism with potential applications for treatment of obesity and insulin resistance.