Role of transcription factor NFAT in glucose and insulin homeostasis

Teddy T C Yang, Hee Yun Suk, Xiao Yong Yang, Opeyemi Olabisi, Raymond Y L Yu, Jorge Durand, Linda A. Jelicks, Ja Young Kim, Philipp E. Scherer, Yuhua Wang, Yun Feng, Luciano Rossetti, Isabella A. Graef, Gerald R. Crabtree, Chi Wing Chow

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Compromised immunoregulation contributes to obesity and complications in metabolic pathogenesis. Here, we demonstrate that the nuclear factor of activated T cell (NFAT) group of transcription factors contributes to glucose and insulin homeostasis. Expression of two members of the NFAT family (NFATc2 and NFATc4) is induced upon adipogenesis and in obese mice. Mice with the Nfatc2-/- Nfatc4-/- compound disruption exhibit defects in fat accumulation and are lean. Nfatc2-/- Nfatc4-/- mice are also protected from diet-induced obesity. Ablation of NFATc2 and NFATc4 increases insulin sensitivity, in part, by sustained activation of the insulin signaling pathway. Nfatc2-/- Nfatc4-/- mice also exhibit an altered adipokine profile, with reduced resistin and leptin levels. Mechanistically, NFAT is recruited to the transcription loci and regulates resistin gene expression upon insulin stimulation. Together, these results establish a role for NFAT in glucose/insulin homeostasis and expand the repertoire of NFAT function to metabolic pathogenesis and adipokine gene transcription.

Original languageEnglish (US)
Pages (from-to)7372-7387
Number of pages16
JournalMolecular and Cellular Biology
Volume26
Issue number20
DOIs
StatePublished - Oct 2006

Fingerprint

NFATC Transcription Factors
Homeostasis
Transcription Factors
Insulin
Glucose
Resistin
Adipokines
Obesity
Obese Mice
Adipogenesis
Leptin
Insulin Resistance
Fats
Diet
Gene Expression
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Yang, T. T. C., Suk, H. Y., Yang, X. Y., Olabisi, O., Yu, R. Y. L., Durand, J., ... Chow, C. W. (2006). Role of transcription factor NFAT in glucose and insulin homeostasis. Molecular and Cellular Biology, 26(20), 7372-7387. https://doi.org/10.1128/MCB.00580-06

Role of transcription factor NFAT in glucose and insulin homeostasis. / Yang, Teddy T C; Suk, Hee Yun; Yang, Xiao Yong; Olabisi, Opeyemi; Yu, Raymond Y L; Durand, Jorge; Jelicks, Linda A.; Kim, Ja Young; Scherer, Philipp E.; Wang, Yuhua; Feng, Yun; Rossetti, Luciano; Graef, Isabella A.; Crabtree, Gerald R.; Chow, Chi Wing.

In: Molecular and Cellular Biology, Vol. 26, No. 20, 10.2006, p. 7372-7387.

Research output: Contribution to journalArticle

Yang, TTC, Suk, HY, Yang, XY, Olabisi, O, Yu, RYL, Durand, J, Jelicks, LA, Kim, JY, Scherer, PE, Wang, Y, Feng, Y, Rossetti, L, Graef, IA, Crabtree, GR & Chow, CW 2006, 'Role of transcription factor NFAT in glucose and insulin homeostasis', Molecular and Cellular Biology, vol. 26, no. 20, pp. 7372-7387. https://doi.org/10.1128/MCB.00580-06
Yang TTC, Suk HY, Yang XY, Olabisi O, Yu RYL, Durand J et al. Role of transcription factor NFAT in glucose and insulin homeostasis. Molecular and Cellular Biology. 2006 Oct;26(20):7372-7387. https://doi.org/10.1128/MCB.00580-06
Yang, Teddy T C ; Suk, Hee Yun ; Yang, Xiao Yong ; Olabisi, Opeyemi ; Yu, Raymond Y L ; Durand, Jorge ; Jelicks, Linda A. ; Kim, Ja Young ; Scherer, Philipp E. ; Wang, Yuhua ; Feng, Yun ; Rossetti, Luciano ; Graef, Isabella A. ; Crabtree, Gerald R. ; Chow, Chi Wing. / Role of transcription factor NFAT in glucose and insulin homeostasis. In: Molecular and Cellular Biology. 2006 ; Vol. 26, No. 20. pp. 7372-7387.
@article{ecea7be508a644989c46b832418b2ce4,
title = "Role of transcription factor NFAT in glucose and insulin homeostasis",
abstract = "Compromised immunoregulation contributes to obesity and complications in metabolic pathogenesis. Here, we demonstrate that the nuclear factor of activated T cell (NFAT) group of transcription factors contributes to glucose and insulin homeostasis. Expression of two members of the NFAT family (NFATc2 and NFATc4) is induced upon adipogenesis and in obese mice. Mice with the Nfatc2-/- Nfatc4-/- compound disruption exhibit defects in fat accumulation and are lean. Nfatc2-/- Nfatc4-/- mice are also protected from diet-induced obesity. Ablation of NFATc2 and NFATc4 increases insulin sensitivity, in part, by sustained activation of the insulin signaling pathway. Nfatc2-/- Nfatc4-/- mice also exhibit an altered adipokine profile, with reduced resistin and leptin levels. Mechanistically, NFAT is recruited to the transcription loci and regulates resistin gene expression upon insulin stimulation. Together, these results establish a role for NFAT in glucose/insulin homeostasis and expand the repertoire of NFAT function to metabolic pathogenesis and adipokine gene transcription.",
author = "Yang, {Teddy T C} and Suk, {Hee Yun} and Yang, {Xiao Yong} and Opeyemi Olabisi and Yu, {Raymond Y L} and Jorge Durand and Jelicks, {Linda A.} and Kim, {Ja Young} and Scherer, {Philipp E.} and Yuhua Wang and Yun Feng and Luciano Rossetti and Graef, {Isabella A.} and Crabtree, {Gerald R.} and Chow, {Chi Wing}",
year = "2006",
month = "10",
doi = "10.1128/MCB.00580-06",
language = "English (US)",
volume = "26",
pages = "7372--7387",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "20",

}

TY - JOUR

T1 - Role of transcription factor NFAT in glucose and insulin homeostasis

AU - Yang, Teddy T C

AU - Suk, Hee Yun

AU - Yang, Xiao Yong

AU - Olabisi, Opeyemi

AU - Yu, Raymond Y L

AU - Durand, Jorge

AU - Jelicks, Linda A.

AU - Kim, Ja Young

AU - Scherer, Philipp E.

AU - Wang, Yuhua

AU - Feng, Yun

AU - Rossetti, Luciano

AU - Graef, Isabella A.

AU - Crabtree, Gerald R.

AU - Chow, Chi Wing

PY - 2006/10

Y1 - 2006/10

N2 - Compromised immunoregulation contributes to obesity and complications in metabolic pathogenesis. Here, we demonstrate that the nuclear factor of activated T cell (NFAT) group of transcription factors contributes to glucose and insulin homeostasis. Expression of two members of the NFAT family (NFATc2 and NFATc4) is induced upon adipogenesis and in obese mice. Mice with the Nfatc2-/- Nfatc4-/- compound disruption exhibit defects in fat accumulation and are lean. Nfatc2-/- Nfatc4-/- mice are also protected from diet-induced obesity. Ablation of NFATc2 and NFATc4 increases insulin sensitivity, in part, by sustained activation of the insulin signaling pathway. Nfatc2-/- Nfatc4-/- mice also exhibit an altered adipokine profile, with reduced resistin and leptin levels. Mechanistically, NFAT is recruited to the transcription loci and regulates resistin gene expression upon insulin stimulation. Together, these results establish a role for NFAT in glucose/insulin homeostasis and expand the repertoire of NFAT function to metabolic pathogenesis and adipokine gene transcription.

AB - Compromised immunoregulation contributes to obesity and complications in metabolic pathogenesis. Here, we demonstrate that the nuclear factor of activated T cell (NFAT) group of transcription factors contributes to glucose and insulin homeostasis. Expression of two members of the NFAT family (NFATc2 and NFATc4) is induced upon adipogenesis and in obese mice. Mice with the Nfatc2-/- Nfatc4-/- compound disruption exhibit defects in fat accumulation and are lean. Nfatc2-/- Nfatc4-/- mice are also protected from diet-induced obesity. Ablation of NFATc2 and NFATc4 increases insulin sensitivity, in part, by sustained activation of the insulin signaling pathway. Nfatc2-/- Nfatc4-/- mice also exhibit an altered adipokine profile, with reduced resistin and leptin levels. Mechanistically, NFAT is recruited to the transcription loci and regulates resistin gene expression upon insulin stimulation. Together, these results establish a role for NFAT in glucose/insulin homeostasis and expand the repertoire of NFAT function to metabolic pathogenesis and adipokine gene transcription.

UR - http://www.scopus.com/inward/record.url?scp=33749636442&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33749636442&partnerID=8YFLogxK

U2 - 10.1128/MCB.00580-06

DO - 10.1128/MCB.00580-06

M3 - Article

VL - 26

SP - 7372

EP - 7387

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 20

ER -