ATM Regulates Adipocyte Differentiation and Contributes to Glucose Homeostasis

• ATM, linked to ataxia telangiectasia, regulates adipocyte differentiation
• The adipocyte differentiation defect in A-T contributes to type 2 diabetes
• Transcriptional activation of C/EBPα and PPARγ depends on ATM
• Binding of ATM to C/EBPβ and p300 induces transcriptional regulation of C/EBPα

SummaryAtaxia-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/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.

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