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

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

Research output: Contribution to journal › Article › peer-review

29 Citations (Scopus)

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, invitro 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 providesinsight into the role of ATM in glucose metabolism.

Original language	English
Pages (from-to)	957-967
Number of pages	11
Journal	Cell Reports
Volume	10
Issue number	6
DOIs	https://doi.org/10.1016/j.celrep.2015.01.027
Publication status	Published - Feb 17 2015
Externally published	Yes

All Science Journal Classification (ASJC) codes

Biochemistry, Genetics and Molecular Biology(all)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.celrep.2015.01.027

Cite this

@article{d214babb79654a6ebb402ca3c25aa4bb,

title = "ATM Regulates Adipocyte Differentiation and Contributes to Glucose Homeostasis",

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, invitro 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 providesinsight into the role of ATM in glucose metabolism.",

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

note = "Funding Information: This study was supported by a Grant-in-Aid from the Ministry of Education, Science, and Culture (grant 11939625), the Ministry of Health, Labor, and Welfare (grant 26310401), the Uehara Foundation, the Sumitomo Foundation, Morinaga Hoshikai, the Takeda Science Foundation, the Suzuken Memorial Foundation, and the Boshi Hoken Kyokai Foundation. We thank Atsuko Nishikawa for technical assistance. The Atm knockout mouse was kindly provided by Dr. Peter McKinnon (St. Jude Children{\textquoteright}s Research Hospital, Memphis, TN). The Atm +/+ and Atm −/− MEF cell lines were kindly provided by Dr. Charles Sherr (St. Jude Children{\textquoteright}s Research Hospital). We thank Hikari Taka and Tsutomu Fujimura (Juntendo University, Tokyo) for performing the LC-MS analysis. We thank Kevin Urayama (Tokyo Medical and Dental University) for critical reading of the manuscript. Publisher Copyright: {\textcopyright} 2015 The Authors.",

year = "2015",

month = feb,

day = "17",

doi = "10.1016/j.celrep.2015.01.027",

language = "English",

volume = "10",

pages = "957--967",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "6",

}

TY - JOUR

T1 - ATM Regulates Adipocyte Differentiation and Contributes to Glucose Homeostasis

AU - Takagi, Masatoshi

AU - Uno, Hatsume

AU - Nishi, Rina

AU - Sugimoto, Masataka

AU - Hasegawa, Setsuko

AU - Piao, Jinhua

AU - Ihara, Norimasa

AU - Kanai, Sayaka

AU - Kakei, Saori

AU - Tamura, Yoshifumi

AU - Suganami, Takayoshi

AU - Kamei, Yasutomi

AU - Shimizu, Toshiaki

AU - Yasuda, Akio

AU - Ogawa, Yoshihiro

AU - Mizutani, Shuki

N1 - Funding Information: This study was supported by a Grant-in-Aid from the Ministry of Education, Science, and Culture (grant 11939625), the Ministry of Health, Labor, and Welfare (grant 26310401), the Uehara Foundation, the Sumitomo Foundation, Morinaga Hoshikai, the Takeda Science Foundation, the Suzuken Memorial Foundation, and the Boshi Hoken Kyokai Foundation. We thank Atsuko Nishikawa for technical assistance. The Atm knockout mouse was kindly provided by Dr. Peter McKinnon (St. Jude Children’s Research Hospital, Memphis, TN). The Atm +/+ and Atm −/− MEF cell lines were kindly provided by Dr. Charles Sherr (St. Jude Children’s Research Hospital). We thank Hikari Taka and Tsutomu Fujimura (Juntendo University, Tokyo) for performing the LC-MS analysis. We thank Kevin Urayama (Tokyo Medical and Dental University) for critical reading of the manuscript. Publisher Copyright: © 2015 The Authors.

PY - 2015/2/17

Y1 - 2015/2/17

N2 - 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, invitro 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 providesinsight into the role of ATM in glucose metabolism.

AB - 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, invitro 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 providesinsight into the role of ATM in glucose metabolism.

UR - http://www.scopus.com/inward/record.url?scp=84923114348&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84923114348&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2015.01.027

DO - 10.1016/j.celrep.2015.01.027

M3 - Article

AN - SCOPUS:84923114348

SN - 2211-1247

VL - 10

SP - 957

EP - 967

JO - Cell Reports

JF - Cell Reports

IS - 6

ER -

ATM Regulates Adipocyte Differentiation and Contributes to Glucose Homeostasis

Abstract

All Science Journal Classification (ASJC) codes

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this