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

46 Scopus citations

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

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Yang, T. T. C., Suk, H. Y., Yang, X. Y., Olabisi, O., Yu, R. Y. L., Durand, J., Jelicks, L. A., Kim, J. Y., Scherer, P. E., Wang, Y., Feng, Y., Rossetti, L., Graef, I. A., Crabtree, G. R., & 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