Nuclear factor of activated T cell (NFAT) transcription proteins regulate genes involved in adipocyte metabolism and lipolysis.
NFAT involvement in adipocyte physiological processes was examined by treatment with CsA and/or GSK3beta inhibitors (Li(+) or TZDZ-8), which prevent or increase NFAT nuclear translocation, respectively. CsA treatment reduced basal and TNFalpha-induced rates of lipolysis by 50%. Adipocytes preincubated with Li(+) or TZDZ-8 prior to CsA and/or TNFalpha, exhibited enhanced basal rates of lipolysis and complete inhibition of CsA-mediated decreased rates of lipolysis. CsA treatment dramatically reduced the mRNA levels of adipocyte-specific genes (aP2, HSL, PPARgamma, ACS and Adn), compared with control or TNFalpha-treatment, whereas Li(+) pretreatment blocked the inhibitory effects of CsA, and mRNA levels of aP2, HSL, PPARgamma, and ACS were found at or above control levels. NFAT nuclear localization, assessed by EMSA, confirmed that CsA or Li(+) treatments inhibited or increased NFAT nuclear translocation, respectively. These results show that NFAT proteins in mature adipocytes participate in the transcriptional control of genes involved in adipocyte metabolism and lipolysis.
Holowachuk
Eugene W
EW
Mary Imogene Bassett Hospital, Research Institute, 1 Atwell Road, Cooperstown, NY 13326, USA. geneh@telenet.net
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D016384:Consensus Sequence; D016572:Cyclosporine / Q000494:pharmacology; D005786:Gene Expression Regulation; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors; D000071679:Glycogen Synthase Kinase 3 beta; D008066:Lipolysis / Q000187:drug effects / Q000235:genetics*; D008094:Lithium / Q000494:pharmacology; D051379:Mice; D050778:NFATC Transcription Factors / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D050778:NFATC Transcription Factors; D047428:Protein Kinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D016572:Cyclosporine; D008094:Lithium; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3