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 journalArticle

9 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 languageEnglish
Pages (from-to)957-967
Number of pages11
JournalCell Reports
Volume10
Issue number6
DOIs
Publication statusPublished - Feb 17 2015

Fingerprint

Automatic teller machines
Adipocytes
Homeostasis
Glucose
Diabetes Mellitus
Medical problems
Ataxia Telangiectasia
Peroxisome Proliferator-Activated Receptors
Glucose Intolerance
Subcutaneous Fat
Adiponectin
Transcription Factors
Metabolism
Insulin
Tissue
Serum

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Takagi, M., Uno, H., Nishi, R., Sugimoto, M., Hasegawa, S., Piao, J., ... Mizutani, S. (2015). ATM Regulates Adipocyte Differentiation and Contributes to Glucose Homeostasis. Cell Reports, 10(6), 957-967. https://doi.org/10.1016/j.celrep.2015.01.027

ATM Regulates Adipocyte Differentiation and Contributes to Glucose Homeostasis. / 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.

In: Cell Reports, Vol. 10, No. 6, 17.02.2015, p. 957-967.

Research output: Contribution to journalArticle

Takagi, M, Uno, H, Nishi, R, Sugimoto, M, Hasegawa, S, Piao, J, Ihara, N, Kanai, S, Kakei, S, Tamura, Y, Suganami, T, Kamei, Y, Shimizu, T, Yasuda, A, Ogawa, Y & Mizutani, S 2015, 'ATM Regulates Adipocyte Differentiation and Contributes to Glucose Homeostasis', Cell Reports, vol. 10, no. 6, pp. 957-967. https://doi.org/10.1016/j.celrep.2015.01.027
Takagi M, Uno H, Nishi R, Sugimoto M, Hasegawa S, Piao J et al. ATM Regulates Adipocyte Differentiation and Contributes to Glucose Homeostasis. Cell Reports. 2015 Feb 17;10(6):957-967. https://doi.org/10.1016/j.celrep.2015.01.027
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. / ATM Regulates Adipocyte Differentiation and Contributes to Glucose Homeostasis. In: Cell Reports. 2015 ; Vol. 10, No. 6. pp. 957-967.
@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",
year = "2015",
month = "2",
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

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

VL - 10

SP - 957

EP - 967

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 6

ER -