Resistin is regulated by C/EBPs, PPARs, and signal-transducing molecules.
Expression of the adipocyte-derived protein resistin, which is thought to play a key role in the development of insulin resistance in vivo, is regulated by a variety of hormones and mediators, including insulin and TNFalpha. Here we describe our use of adenovirus-mediated gene transfer to determine which transcription factors and signaling pathways affect resistin expression in 3T3-L1 adipocytes. We found that resistin expression was enhanced by overexpression of C/EBPalpha and suppressed by C/EBPzeta, a negative regulator of C/EBPalpha. Additionally, C/EBPalpha induced resistin even in L6 myocytes. Overexpression of PPARgamma markedly reduced resistin expression, whereas PPARalpha had no significant effect. Resistin expression was markedly suppressed by overexpression of the PI3-kinase p110alpha catalytic subunit and by Akt. Finally, overexpression of MEK1, MKK6, or MKK7 suppressed resistin expression. These findings indicate that resistin expression is regulated by C/EBPalpha and PPARgamma, partly via modulation of signal transduction in the PI3-kinase and MAP kinase pathways.
Song
Haiyan
H
Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113, Tokyo, Japan.
Shojima
Nobuhiro
N
Sakoda
Hideyuki
H
Ogihara
Takehide
T
Fujishiro
Midori
M
Katagiri
Hideki
H
Anai
Motonobu
M
Onishi
Yukiko
Y
Ono
Hiraku
H
Inukai
Kouichi
K
Fukushima
Yasushi
Y
Kikuchi
Masatoshi
M
Shimano
Hitoshi
H
Yamada
Nobuhiro
N
Oka
Yoshitomo
Y
Asano
Tomoichiro
T
D016475:3T3 Cells; D000256:Adenoviridae / Q000235:genetics; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000502:physiology; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D006729:Hormones, Ectopic / Q000096:biosynthesis / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000502:physiology; D020932:Nerve Growth Factor; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000502:physiology; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000502:physiology; D017346:Protein Serine-Threonine Kinases; D011506:Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger / Q000096:biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000502:physiology*; D052243:Resistin; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology
D022763:CCAAT-Enhancer-Binding Protein-alpha; D022762:CCAAT-Enhancer-Binding Proteins; D006729:Hormones, Ectopic; D036341:Intercellular Signaling Peptides and Proteins; D020928:Mitogen-Activated Protein Kinases; D020932:Nerve Growth Factor; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D010744:Phosphoric Monoester Hydrolases; D017346:Protein Serine-Threonine Kinases; D011506:Proteins; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D052243:Resistin; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C486574:RETNLB protein, human; C499623:Retn protein, mouse; C413576:Retnla protein, mouse