A family of Acrp30/adiponectin structural and functional paralogs
A family of Acrp30/adiponectin structural and functional paralogs
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DOI：
10.1073/pnas.0403760101
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发表时间：
2004-07-13
影响因子：
11.1
通讯作者：
Lodish, HF
中科院分区：
文献类型：
--
作者：
Wong, GW;Wang, J;Lodish, HF
近年来，生化、遗传学和动物研究证实，脂肪因子Acrp30/脂联素在控制全身代谢中起着关键作用，特别是通过增强肌肉和肝脏的胰岛素敏感性，以及通过增加肌肉中的脂肪酸氧化。我们描述了一个广泛表达和高度保守的脂联素类似物家族，命名为C1q/肿瘤坏死因子-α相关蛋白(CTRPs)1-7。在目前的研究中，我们将重点放在mCTRP2上，这是一种与脂联素最相似的小鼠类似基因。在纳摩尔浓度下，细菌产生的mCTRP2迅速诱导C2C12肌管中AMP激活的蛋白激酶、乙酰辅酶A羧化酶和丝裂原激活的蛋白激酶的磷酸化，导致糖原积累和脂肪酸氧化增加。脂联素家族的发现对理解能量稳态的控制具有重要意义，并可能为糖尿病和肥胖症等代谢性疾病的药物干预提供新的靶点。
Biochemical, genetic, and animal studies in recent years have established a critical role for the adipokine Acrp30/adiponectin in controlling whole-body metabolism, particularly by enhancing insulin sensitivity in muscle and liver, and by increasing fatty acid oxidation in muscle. We describe a widely expressed and highly conserved family of adiponectin paralogs designated as C1q/ tumor necrosis factor-alpha-related proteins (CTRPs) 1-7. In the present study, we focus on mCTRP2, the mouse paralog most similar to adiponectin. At nanomolar concentrations, bacterially produced mCTRP2 rapidly induced phosphorylation of AMP-activated protein kinase, acetyl-CoA carboxylase, and mitogen-activated protein kinase in C2C12 myotubes, which resulted in increased glycogen accumulation and fatty acid oxidation. The discovery of a family of adiponectin paralogs has implications for understanding the control of energy homeostasis and could provide new targets for pharmacologic intervention in metabolic diseases such as diabetes and obesity.