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.
authors.affiliation: Department of Molecular Pharmacology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461, USA.
authors.forename: Teddy T C
authors.initials: TT
authors.lastname: Yang
authors.forename: Hee Yun
authors.initials: HY
authors.lastname: Suk
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Yang
authors.forename: Opeyemi
authors.initials: O
authors.lastname: Olabisi
authors.forename: Raymond Y L
authors.initials: RY
authors.lastname: Yu
authors.forename: Jorge
authors.initials: J
authors.lastname: Durand
authors.forename: Linda A
authors.initials: LA
authors.lastname: Jelicks
authors.forename: Ja-Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Philipp E
authors.initials: PE
authors.lastname: Scherer
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Wang
authors.forename: Yun
authors.initials: Y
authors.lastname: Feng
authors.forename: Luciano
authors.initials: L
authors.lastname: Rossetti
authors.forename: Isabella A
authors.initials: IA
authors.lastname: Graef
authors.forename: Gerald R
authors.initials: GR
authors.lastname: Crabtree
authors.forename: Chi-Wing
authors.initials: CW
authors.lastname: Chow
mesh_terms: D055372:AMP-Activated Protein Kinases; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002522:Chlorocebus aethiops; D004041:Dietary Fats / Q000494:pharmacology; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009097:Multienzyme Complexes / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D052243:Resistin / Q000378:metabolism; D012680:Sensitivity and Specificity; D015398:Signal Transduction
chemical_list: D004041:Dietary Fats; D007328:Insulin; D009097:Multienzyme Complexes; D050778:NFATC Transcription Factors; D052243:Resistin; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D005947:Glucose