Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

Mol. Cell. Biol. 26 (20): 7372-7387

Copyright © 2006 by the American Society for Microbiology. All rights reserved.

Role of Transcription Factor NFAT in Glucose and Insulin Homeostasis{triangledown}

Teddy T. C. Yang,1 Hee Yun Suk,1 XiaoYong Yang,1 Opeyemi Olabisi,1 Raymond Y. L. Yu,1 Jorge Durand,2 Linda A. Jelicks,2 Ja-Young Kim,3 Philipp E. Scherer,3,4 Yuhua Wang,4 Yun Feng,4 Luciano Rossetti,1,4 Isabella A. Graef,5 Gerald R. Crabtree,5, and Chi-Wing Chow1*

Department of Molecular Pharmacology,1 Department of Physiology and Biophysics,2 Department of Cell Biology,3 Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461,4 Department of Developmental Biology and Department of Pathology, Howard Hughes Medical Institute, Stanford University Medical School, Stanford, California 943055

Received for publication 3 April 2006. Revision received 16 May 2006. Accepted for publication 2 August 2006.

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.

* Corresponding author. Mailing address: Department of Molecular Pharmacology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461. Phone: (718) 430-2716. Fax: (718) 430-8922. E-mail: cchow{at}aecom.yu.edu.

{triangledown} Published ahead of print on 14 August 2006.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Ablation of Calcineurin A{beta} Reveals Hyperlipidemia and Signaling Cross-talks with Phosphodiesterases.
H. Y. Suk, C. Zhou, T. T. C. Yang, H. Zhu, R. Y. L. Yu, O. Olabisi, X. Yang, D. Brancho, J.-Y. Kim, P. E. Scherer, et al. (2013)
J. Biol. Chem. 288, 3477-3488
   Abstract »    Full Text »    PDF »
Molecular Diagnostics of Calcineurin-Related Pathologies.
R. E. A. Musson, C. M. Cobbaert, and N. P. M. Smit (2012)
Clin. Chem. 58, 511-522
   Abstract »    Full Text »    PDF »
Genetic Defect in Phospholipase C{delta}1 Protects Mice From Obesity by Regulating Thermogenesis and Adipogenesis.
M. Hirata, M. Suzuki, R. Ishii, R. Satow, T. Uchida, T. Kitazumi, T. Sasaki, T. Kitamura, H. Yamaguchi, Y. Nakamura, et al. (2011)
Diabetes 60, 1926-1937
   Abstract »    Full Text »    PDF »
Nuclear factor of activated T cells (NFAT) signaling regulates PTEN expression and intestinal cell differentiation.
Q. Wang, Y. Zhou, L. N. Jackson, S. M. Johnson, C.-W. Chow, and B. M. Evers (2011)
Mol. Biol. Cell 22, 412-420
   Abstract »    Full Text »    PDF »
Evolutionarily Conserved Role of Calcineurin in Phosphodegron-Dependent Degradation of Phosphodiesterase 4D.
H. Zhu, H. Y. Suk, R. Y. L. Yu, D. Brancho, O. Olabisi, T. T. C. Yang, X. Yang, J. Zhang, M. Moussaif, J. L. Durand, et al. (2010)
Mol. Cell. Biol. 30, 4379-4390
   Abstract »    Full Text »    PDF »
Lipin 1 Represses NFATc4 Transcriptional Activity in Adipocytes To Inhibit Secretion of Inflammatory Factors.
H. B. Kim, A. Kumar, L. Wang, G. H. Liu, S. R. Keller, J. C. Lawrence Jr., B. N. Finck, and T. E. Harris (2010)
Mol. Cell. Biol. 30, 3126-3139
   Abstract »    Full Text »    PDF »
Chromatin-bound mitogen-activated protein kinases transmit dynamic signals in transcription complexes in {beta}-cells.
M. C. Lawrence, K. McGlynn, C. Shao, L. Duan, B. Naziruddin, M. F. Levy, and M. H. Cobb (2008)
PNAS 105, 13315-13320
   Abstract »    Full Text »    PDF »
Integration of Protein Kinases mTOR and Extracellular Signal-Regulated Kinase 5 in Regulating Nucleocytoplasmic Localization of NFATc4.
T. T. C. Yang, R. Y. L. Yu, A. Agadir, G.-J. Gao, R. Campos-Gonzalez, C. Tournier, and C.-W. Chow (2008)
Mol. Cell. Biol. 28, 3489-3501
   Abstract »    Full Text »    PDF »
Conditional Disruption of Calcineurin B1 in Osteoblasts Increases Bone Formation and Reduces Bone Resorption.
H. Yeo, L. H. Beck, S. R. Thompson, M. C. Farach-Carson, J. M. McDonald, T. L. Clemens, and M. Zayzafoon (2007)
J. Biol. Chem. 282, 35318-35327
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882