ATM Regulates Adipocyte Differentiation and Contributes to Glucose Homeostasis

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

doi:10.1016/j.celrep.2015.01.027

ATM Regulates Adipocyte Differentiation and Contributes to Glucose Homeostasis

Cell Rep. 2015 Feb 17;10(6):957-967. doi: 10.1016/j.celrep.2015.01.027. Epub 2015 Feb 12.

Authors

Affiliations

¹ Department of Pediatrics and Developmental Biology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. Electronic address: m.takagi.ped@tmd.ac.jp.
² Department of Pediatrics and Developmental Biology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan; Medical Business Unit, Sony Corporation, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
³ Department of Pediatrics and Developmental Biology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
⁴ Section of Biochemistry, National Institute for Longevity Sciences, NCGG, 36-3 Gengo, Moriokacho, Obu, Aichi 474-8522, Japan.
⁵ Department of Reproductive Biology, National Research Institute for Child Health and Development, 2-10-1 Ohkura, Setagaya-ku, Tokyo 157-0074, Japan.
⁶ Department of Molecular Endocrinology and Metabolism, Graduate School of Medicine, Tokyo Medical and Dental University, Japan Science and Technology Agency, CREST, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
⁷ Department of Medicine, Metabolism & Endocrinology, Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
⁸ Department of Organ Network and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Japan Science and Technology Agency, PRESTO, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
⁹ Laboratory of Molecular Nutrition, Graduate School of Environmental and Life Science, Kyoto Prefectural University, Hangicho 1-5, Shimogamo, Kyotoshi, Kyoto 606-8522, Japan.
¹⁰ Department of Pediatrics and Adolescent Medicine, Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

PMID: 25683718
DOI: 10.1016/j.celrep.2015.01.027

Abstract

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/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.