Okuno Yosuke, Matsuda Morihiro, Kobayashi Hironori, Morita Kentaro, Suzuki Emi, Fukuhara Atsunori, Komuro Ryutaro, Shimabukuro Michio, Shimomura Iichiro
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Biochem Biophys Res Commun. 2008 Feb 15;366(3):698-704. doi: 10.1016/j.bbrc.2007.12.001. Epub 2007 Dec 10.
In adipose tissue of obese mice, the expression of catalase, an anti-oxidant enzyme, significantly decreases, which may cause insufficient elimination of hydrogen peroxide, but it does not in liver or skeletal muscle. However, the precise regulatory mechanism of catalase expression in adipocytes has not been fully defined. Here, we demonstrated that adipose tissues highly expressed catalase on the level comparable to liver and kidney, and treatment of mice with PPARgamma agonist significantly enhanced catalase expression in adipose tissue but not in liver. In 3T3-L1 cells, mRNA expression of catalase was up-regulated by the induction for adipose differentiation, and down-regulated by TNFalpha, in parallel with alterations in PPARgamma expression. PPARgamma agonist significantly enhanced catalase mRNA and activity. Furthermore, we newly identified a remote enhancer region containing two functional PPARgamma binding sites in mouse catalase gene. Collectively, our findings suggest that PPARgamma plays a crucial role in the expression of catalase in adipocytes.
在肥胖小鼠的脂肪组织中,抗氧化酶过氧化氢酶的表达显著降低,这可能导致过氧化氢清除不足,但在肝脏或骨骼肌中并非如此。然而,脂肪细胞中过氧化氢酶表达的确切调控机制尚未完全明确。在此,我们证明脂肪组织中过氧化氢酶的表达水平与肝脏和肾脏相当,用PPARγ激动剂处理小鼠可显著增强脂肪组织中过氧化氢酶的表达,但对肝脏无此作用。在3T3-L1细胞中,过氧化氢酶的mRNA表达随脂肪分化诱导而上调,随TNFα作用而下调,与PPARγ表达的变化平行。PPARγ激动剂显著增强过氧化氢酶的mRNA水平和活性。此外,我们新发现了小鼠过氧化氢酶基因中一个包含两个功能性PPARγ结合位点的远端增强子区域。总之,我们的研究结果表明PPARγ在脂肪细胞中过氧化氢酶的表达中起关键作用。