ATM Regulates Adipocyte Differentiation and Contributes to Glucose Homeostasis

作者：Takagi Masatoshi^*; Uno Hatsume; Nishi Rina; Sugimoto Masataka; Hasegawa Setsuko; Piao Jinhua; Ihara Norimasa; Kanai Sayaka; Kakei Saori; Tamura Yoshifumi; Suganami Takayoshi; Kamei Yasutomi; Shimizu Toshiaki; Yasuda Akio; Ogawa Yoshihiro; Mizutani Shuki

来源：Cell Reports, 2015, 10(6): 957-967.

DOI：10.1016/j.celrep.2015.01.027

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 that Atm(-/-) mice were insulin resistant and possessed less subcutaneous adipose tissue as well as a lower level of serum adiponectin than Atm(+/+) mice. Furthermore, in vitro studies revealed impaired adipocyte differentiation in Atm(-/-) cells caused by the lack of induction of C/EBP alpha and PPAR gamma, crucial transcription factors involved in adipocyte differentiation. Interestingly, ATM was activated by stimuli that induced differentiation, and the binding of ATM to C/EBP beta and p300 was involved in the transcriptional regulation of C/EBP alpha 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.

• 出版日期2015-2-17