Transcriptional regulation of an insulin-sensitizing adipokine adipolin/CTRP12 in adipocytes by Krüppel-like factor 15.
Transcriptional regulation of an insulin-sensitizing adipokine adipolin/CTRP12 in adipocytes by Krüppel-like factor 15.
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DOI：
10.1371/journal.pone.0083183
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Ouchi N
中科院分区：
文献类型：
--
作者：
Enomoto T;Ohashi K;Shibata R;Kambara T;Uemura Y;Yuasa D;Kataoka Y;Miyabe M;Matsuo K;Joki Y;Hayakawa S;Hiramatsu-Ito M;Ito M;Murohara T;Ouchi N
以慢性炎症为特征的肥胖状态与代谢功能障碍的发展密切相关。我们确定adipolin/CTRP 12作为胰岛素增敏和抗炎脂肪因子。虽然肥胖条件下adipolin表达下调，其分子机制在很大程度上是未知的。在这里，我们表明，转录调节Krüppel样因子（KLF）15参与调节脂肪细胞中adipolin的表达。饮食诱导肥胖（DIO）小鼠的白色脂肪组织显示，在几种KLF中，KLF 9和KLF 15的表达降低，这伴随着adipolin的表达降低。在培养的3 T3 L1脂肪细胞中，TNFα处理显著降低KLF 9、KLF 15和adipolin的mRNA水平。腺病毒介导的KLF 15而非KLF 9的过表达逆转了TNFα诱导的脂肪细胞中adipolin表达的减少。相反，KLF 15的基因靶向消融减弱了脂肪细胞中adipolin的表达。在HEK 293细胞中，KLF 15而非KLF 9的表达增强了adipolin的启动子活性。用JNK抑制剂SP 600125预处理3 T3 L1脂肪细胞可阻断TNFα对adipolin和KLF 15表达的抑制作用，但p38 MAPK抑制剂SB 203580不能阻断TNFα对adipolin和KLF 15表达的抑制作用。这些数据表明，肥胖条件下的脂肪炎症通过JNK依赖性下调脂肪细胞中的KLF 15来抑制adipolin表达。
Obese states characterized by chronic inflammation are closely linked to the development of metabolic dysfunction. We identified adipolin/CTRP12 as an insulin-sensitizing and anti-inflammatory adipokine. Although obese conditions down-regulate adipolin expression, its molecular mechanism is largely unknown. Here we show that the transcriptional regulator Krüppel-like factor (KLF) 15 is involved in the regulation of adipolin expression in adipocytes. White adipose tissue from diet-induced obese (DIO) mice showed decreased expression of KLF9 and KLF15 among several KLFs, which was accompanied by reduced expression of adipolin. In cultured 3T3L1 adipocytes, treatment with TNFα significantly reduced the mRNA levels of KLF9, KLF15 and adipolin. Adenovirus-mediated overexpression of KLF15 but not KLF9 reversed TNFα-induced reduction of adipolin expression in adipocytes. Conversely, gene targeting ablation of KLF15 attenuated adipolin expression in adipocytes. Expression of KLF15 but not KLF9 enhanced the promoter activity of adipolin in HEK293 cells. Pretreatment of 3T3L1 adipocytes with the JNK inhibitor SP600125, but not p38 MAPK inhibitor SB203580 blocked the inhibitory effects of TNFα on adipolin and KLF15 expression. These data suggest that adipose inflammation under conditions of obesity suppresses adipolin expression via JNK-dependent down-regulation of KLF15 in adipocytes.
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影响因子：
64.5
作者：
Moore KJ;Tabas I
通讯作者：
Tabas I
炎症和代谢疾病中的脂肪因子。
DOI：
10.1038/nri2921
发表时间：
2011-02
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
7.7
作者：
Bell-Anderson KS;Funnell AP;Williams H;Mat Jusoh H;Scully T;Lim WF;Burdach JG;Mak KS;Knights AJ;Hoy AJ;Nicholas HR;Sainsbury A;Turner N;Pearson RC;Crossley M
通讯作者：
Crossley M
影响因子：
82.9
作者：
Maeda, N;Shimomura, I;Matsuzawa, Y
通讯作者：
Matsuzawa, Y
影响因子：
8.3
作者：
Ohashi, Koji;Kihara, Shinji;Shimomura, Iichiro
通讯作者：
Shimomura, Iichiro