Song Haiyan, Shojima Nobuhiro, Sakoda Hideyuki, Ogihara Takehide, Fujishiro Midori, Katagiri Hideki, Anai Motonobu, Onishi Yukiko, Ono Hiraku, Inukai Kouichi, Fukushima Yasushi, Kikuchi Masatoshi, Shimano Hitoshi, Yamada Nobuhiro, Oka Yoshitomo, Asano Tomoichiro
Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113, Tokyo, Japan.
Biochem Biophys Res Commun. 2002 Nov 29;299(2):291-8. doi: 10.1016/s0006-291x(02)02551-2.
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.
脂肪细胞衍生蛋白抵抗素被认为在体内胰岛素抵抗的发展中起关键作用，其表达受多种激素和介质调节，包括胰岛素和肿瘤坏死因子α。在此，我们描述了利用腺病毒介导的基因转移来确定哪些转录因子和信号通路影响3T3-L1脂肪细胞中抵抗素的表达。我们发现，C/EBPα的过表达增强了抵抗素的表达，而C/EBPζ（C/EBPα的负调节因子）则抑制了抵抗素的表达。此外，C/EBPα即使在L6肌细胞中也能诱导抵抗素表达。PPARγ的过表达显著降低了抵抗素的表达，而PPARα则没有显著影响。PI3激酶p110α催化亚基和Akt的过表达显著抑制了抵抗素的表达。最后，MEK1、MKK6或MKK7的过表达抑制了抵抗素的表达。这些发现表明，抵抗素的表达受C/EBPα和PPARγ调节，部分是通过调节PI3激酶和丝裂原活化蛋白激酶途径中的信号转导实现的。
