Differential expression of adrenomedullin and resistin in 3T3-L1 adipocytes treated with tumor necrosis factor-α

Yin Li, Kazuhito Totsune, Kazuhisa Takeda, Kazumichi Furuyama, Shigeki Shibahara, Kazuhiro Takahashi

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)

Abstract

Design: 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-α (TNF-α), 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-α 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-α 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-α may also have actions against insulin resistance through AM and resistin.

Original languageEnglish
Pages (from-to)231-238
Number of pages8
JournalEuropean Journal of Endocrinology
Volume149
Issue number3
DOIs
Publication statusPublished - 2003 Sep 1

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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