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
Affiliations
Masatoshi Takagi
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
Hatsume Uno
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
Rina Nishi
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
Masataka Sugimoto
Section of Biochemistry, National Institute for Longevity Sciences, NCGG, 36-3 Gengo, Moriokacho, Obu, Aichi 474-8522, Japan
Setsuko Hasegawa
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
Jinhua Piao
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
Norimasa Ihara
Department of Reproductive Biology, National Research Institute for Child Health and Development, 2-10-1 Ohkura, Setagaya-ku, Tokyo 157-0074, Japan
Sayaka Kanai
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
Saori Kakei
Department of Medicine, Metabolism & Endocrinology, Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
Yoshifumi Tamura
Department of Medicine, Metabolism & Endocrinology, Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
Takayoshi Suganami
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
Yasutomi Kamei
Laboratory of Molecular Nutrition, Graduate School of Environmental and Life Science, Kyoto Prefectural University, Hangicho 1-5, Shimogamo, Kyotoshi, Kyoto 606-8522, Japan
Toshiaki Shimizu
Department of Pediatrics and Adolescent Medicine, Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Akio Yasuda
Section of Biochemistry, National Institute for Longevity Sciences, NCGG, 36-3 Gengo, Moriokacho, Obu, Aichi 474-8522, Japan
Yoshihiro Ogawa
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
Shuki Mizutani
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
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.
