title: Differential expression of adrenomedullin and resistin in 3T3-L1 adipocytes treated with tumor necrosis factor-alpha.
abstract: METHODS
  It has recently been shown that deficiency of adrenomedullin (AM), a potent vasodilator peptide, leads to insulin resistance. We studied expression of AM in NIH 3T3-L1 adipocytes and compared it with expression of resistin, an adipocyte-derived peptide hormone that is proposed to cause insulin resistance. Moreover, we studied the effects of tumor necrosis factor-alpha (TNF-alpha), a known mediator of insulin resistance, on the expression of AM and resistin in 3T3-L1 adipocytes.
  
  
  METHODS
  3T3-L1 cells were induced to differentiate to adipocytes by insulin, dexamethasone and 3-isobutyl-1-methylxanthine. Expression of AM mRNA and resistin mRNA was examined by Northern blot analysis. Immunoreactive AM in the medium was measured by RIA.
  
  
  RESULTS
  AM mRNA was expressed in preadipocytes, but barely detectable in adipocytes. Immunoreactive AM was detected in the medium of both preadipocytes and adipocytes, with about 2.5 times higher levels found in preadipocytes. In contrast, resistin mRNA was expressed in adipocytes, whereas it was not detected in preadipocytes. Treatment with TNF-alpha increased AM expression in both adipocytes and preadipocytes, whereas it decreased resistin mRNA levels in adipocytes.
  
  
  CONCLUSIONS
  The present study has shown that AM expression was down-regulated and resistin expression was up-regulated during adipocyte differentiation of 3T3-L1 cells. TNF-alpha acted as a potent negative regulator of resistin expression and a potent positive regulator of AM expression in adipocytes, raising the possibility that in addition to its known actions in causing insulin resistance, TNF-alpha may also have actions against insulin resistance through AM and resistin.
authors.affiliation: Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan.
authors.forename: Yin
authors.initials: Y
authors.lastname: Li
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Totsune
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Takeda
authors.forename: Kazumichi
authors.initials: K
authors.lastname: Furuyama
authors.forename: Shigeki
authors.initials: S
authors.lastname: Shibahara
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takahashi
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism*; D053607:Adrenomedullin; D000818:Animals; D015152:Blotting, Northern; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D006729:Hormones, Ectopic / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins; D016898:Interferon-alpha / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D051379:Mice; D020932:Nerve Growth Factor; D010455:Peptides / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D011506:Proteins; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D052243:Resistin; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D005938:Glucocorticoids; D006729:Hormones, Ectopic; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D016898:Interferon-alpha; D007375:Interleukin-1; D010455:Peptides; D011506:Proteins; C499624:RETN protein, human; C486574:RETNLB protein, human; D012333:RNA, Messenger; D011994:Recombinant Proteins; D052243:Resistin; C499623:Retn protein, mouse; C413576:Retnla protein, mouse; D014409:Tumor Necrosis Factor-alpha; D053607:Adrenomedullin; D003907:Dexamethasone; D020932:Nerve Growth Factor; D015056:1-Methyl-3-isobutylxanthine