Regulation of adipolin/CTRP12 cleavage by obesity
Regulation of adipolin/CTRP12 cleavage by obesity
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DOI：
10.1016/j.bbrc.2012.10.031
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发表时间：
2012-11-09
影响因子：
3.1
通讯作者：
Ouchi, Noriyuki
中科院分区：
文献类型：
--
作者：
Enomoto, Takashi;Shibata, Rei;Ouchi, Noriyuki
肥胖与胰岛素抵抗和2型糖尿病的发展高度相关。最近我们发现adipolin/CRTP 12是一种脂肪细胞因子，对葡萄糖代谢发挥有益作用。在这里，我们研究了肥胖条件下循环adipolin的调节，并评估其潜在的机制。在小鼠血浆中观察到完整和裂解形式的脂蛋白。与对照小鼠相比，饮食诱导的肥胖（DIO）小鼠显示完全和总（完全和裂解）脂蛋白的血浆水平显著降低，导致裂解与完全亚型的比值增加。体外基因转染HEK 293细胞的研究表明，adipolin基因的缺失突变体（Δ aa 90 -93）导致培养基中adipolin的裂解产生减少。对adipolin氨基酸序列的生物信息学分析表明，前蛋白转化酶（PC）家族可能参与adipolin的切割。用PC的抑制剂处理3 T3-L1脂肪细胞可消除培养基中裂解的adipolin形式的表达。在DID小鼠的脂肪组织中，前体蛋白家族成员furin的表达增加。弗林蛋白酶的表达也增加了培养的脂肪细胞的治疗与诱导剂的炎症。这些数据表明，肥胖状态可能通过上调脂肪组织中的弗林蛋白酶促进adipolin的裂解。(C)2012 Elsevier Inc. All rights reserved.
Obesity is highly associated with the development of insulin resistance and type 2 diabetes. Recently we found that adipolin/CRTP12 is an adipocytokine that exerts beneficial actions on glucose metabolism. Here we investigated the regulation of circulating adipolin under conditions of obesity and assessed its potential mechanisms. Both full and cleaved forms of adipolin were observed in mouse plasma. Diet-induced obese (DIO) mice showed a significant reduction of plasma levels of full and total (full and cleaved) adipolin compared with control mice, resulting in an increase in the ratio of cleaved to full isoform. In vitro gene transfection studies using HEK293 cells revealed that a deletion mutant of adipolin gene (Delta aa90-93) caused a reduction of cleaved production of adipolin in media. A bioinformatics analysis of adipolin amino acid sequence indicated the potential involvement of the family of proprotein convertases (PCs) in cleavage of adipolin. Treatment of 3T3-L1 adipocytes with an inhibitor for PCs abolished the expression of cleaved adipolin form in the media. The expression of furin, the member of PCs, was increased in adipose tissue of DID mice. Furin expression was also increased in cultured adipocytes by treatment with an inducer of inflammation. These data suggest that obesity states facilitate the cleavage of adipolin presumably through upregulation of furin in adipose tissue. (C) 2012 Elsevier Inc. All rights reserved.