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 TNFα. 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/EBPα and suppressed by C/EBPζ, a negative regulator of C/EBPα. Additionally, C/EBPα induced resistin even in L6 myocytes. Overexpression of PPARγ markedly reduced resistin expressi on, whereas PPARα had no significant effect. Resistin expression was markedly suppressed by overexpression of the PI3-kinase p110α 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/EBPα and PPARγ, partly via modulation of signal transduction in the PI3-kinase and MAP kinase pathways.
|Number of pages||8|
|Journal||Biochemical and Biophysical Research Communications|
|Publication status||Published - 2002|
- Adipogenesis PPARs
- MAP kinase
- Signal transduction