ATM regulates adipocyte differentiation and contributes to glucose homeostasis.
ATM regulates adipocyte differentiation and contributes to glucose homeostasis.
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ATM 调节脂肪细胞分化并有助于葡萄糖稳态。
DOI：
10.1016/j.celrep.2015.01.027
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发表时间：
2015
期刊：
影响因子：
8.8
通讯作者：
Mizutani S.
中科院分区：
文献类型：
--
作者：
Takagi M.;Uno M.;Nishii R.;Sugimoto M.;Hasegawa S.;Piao J.;Ihara N.;Kanai S.;Kakei S.;Tamura Y.;Suganami T.;Kamei Y.;Shimizu T.;Yasuda A.;Ogawa Y.;Mizutani S.
共济失调毛细血管扩张（A-T）患者偶尔会患上糖尿病。然而，只有有限的尝试来深入了解 A-T 患者糖尿病发展的分子机制。我们发现Atm−/−小鼠比Atm+/+小鼠具有胰岛素抵抗性，皮下脂肪组织较少，血清脂联素水平较低。此外，体外研究表明，由于缺乏 C/EBPα 和 PPARγ（参与脂肪细胞分化的关键转录因子）的诱导，Atm−/− 细胞中的脂肪细胞分化受损。有趣的是，ATM 被诱导分化的刺激激活，并且 ATM 与 C/EBPβ 和 p300 的结合参与了 C/EBPα 的转录调节和脂肪细胞分化。因此，我们的研究揭示了人们对 ATM 在 A-T 患者葡萄糖不耐受发病机制中的作用知之甚少，并深入了解了 ATM 在葡萄糖代谢中的作用。
Ataxia-telangiectasia (A-T) patients occasionally develop diabetes mellitus. However, only limited attempts have been made to gain insight into the molecular mechanism of diabetes mellitus development in A-T patients. We found thatAtm−/−mice were insulin resistant and possessed less subcutaneous adipose tissue as well as a lower level of serum adiponectin thanAtm+/+mice. Furthermore, in vitro studies revealed impaired adipocyte differentiation inAtm−/−cells caused by the lack of induction of C/EBPα and PPARγ, crucial transcription factors involved in adipocyte differentiation. Interestingly, ATM was activated by stimuli that induced differentiation, and the binding of ATM to C/EBPβ and p300 was involved in the transcriptional regulation of C/EBPα and adipocyte differentiation. Thus, our study sheds light on the poorly understood role of ATM in the pathogenesis of glucose intolerance in A-T patients and provides insight into the role of ATM in glucose metabolism.