A human-specific role of cell death-inducing DFFA (DNA fragmentation factor-α-like effector A (CIDEA) in adipocyte lipolysis and obesity
A human-specific role of cell death-inducing DFFA (DNA fragmentation factor-α-like effector A (CIDEA) in adipocyte lipolysis and obesity
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DOI：
10.2337/diabetes.54.6.1726
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发表时间：
2005-06-01
期刊：
影响因子：
7.7
通讯作者：
Arner, P
中科院分区：
文献类型：
--
作者：
Nordström, EA;Rydén, M;Arner, P
循环脂肪酸浓度升高是胰岛素抵抗的标志，至少部分归因于脂肪组织来源的肿瘤坏死因子-α（TNF-α）对脂解的作用。细胞死亡诱导DFFA（DNA片段化因子-α）样效应子A（CIDER）属于促凋亡蛋白家族，在人类和小鼠中有五个已知成员。CIDER的作用尚不清楚，但CIDER缺失小鼠对肥胖和糖尿病具有抵抗力。我们研究了肥胖和瘦的人和小鼠的脂肪组织中的CIDER。该mRNA在白色人脂肪细胞和棕色小鼠脂肪细胞中表达。肥胖对小鼠脂肪CIDER mRNA表达无影响。然而，CIDER表达在肥胖人群中降低了两倍，并在体重减轻后恢复正常。低脂肪CIDER表达与代谢综合征的几个特征相关。人脂肪细胞通过RNA干扰去除CIDER刺激脂解，并通过转录后效应增加TNF-α分泌。相反，TNF-α治疗通过丝裂原活化蛋白激酶c-Jun NH 2-末端激酶降低脂肪细胞CIDER表达。我们提出CIDER在脂肪分解调节和肥胖代谢并发症中具有重要且人类特异性的作用，这至少部分是由CIDER和TNF-alpha之间的串扰介导的。
Elevated circulating fatty acid concentration is a hallmark of insulin resistance and is at least in part attributed to the action of adipose tissue-derived tumor necrosis factor-alpha (TNF-alpha) on lipolysis. Cell death-inducing DFFA (DNA fragmentation factor-alpha)-like effector A (CIDER) belongs to a family of proapoptotic proteins that has five known members in humans and mice. The action of CIDER is unknown, but CIDER-null mice are resistant to obesity and diabetes. We investigated CIDER in adipose tissue of obese and lean humans and mice. The mRNA was expressed in white human fat cells and in brown mouse adipocytes. The adipose mRNA expression of CIDER in mice was not influenced by obesity. However, CIDER expression was decreased twofold in obese humans and normalized after weight reduction. Low adipose CIDER expression was associated with several features of the metabolic syndrome. Human adipocyte depletion of CIDER by RNA interference stimulated lipolysis and increased TNF-alpha secretion by a posttranscriptional effect. Conversely, TNF-alpha treatment decreased adipocyte CIDER expression via the mitogen-activated protein kinase c-Jun NH2-terminal kinase. We propose an important and human-specific role for CIDER in lipolysis regulation and metabolic complications of obesity, which is at least in part mediated by cross-talk between CIDER and TNF-alpha.