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标题：Thiazolidinediones Are Potent Inducers of Fibroblast Growth Factor 21 Expression in the Liver
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作者：Katsutaka Oishi ; Tatsunosuke Tomita
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2011
卷号：34
期号：7
页码：1120-1121
DOI：10.1248/bpb.34.1120
出版社：The Pharmaceutical Society of Japan
摘要：Fibroblast growth factor 21 (FGF21) is an effective metabolic regulator of glucose and lipid homeostasis in the context of insulin resistance, glucose intolerance and dyslipidemia in diabetic rodents and monkeys, and peroxisome proliferator-activated receptor α (PPARα) directly induces FGF21 expression in the rodent liver. Recent findings suggest that the effects and regulation of FGF21 qualitatively differ between rodents and humans. Here, we examined the effects of PPARα and PPARγ agonists on FGF21 mRNA expression in the mouse liver and in cultured hepatocytes. Intraperitoneal injection of both bezafibrate and pioglitazone induced FGF21 mRNA expression in the mouse liver. Rosiglitazone and pioglitazone as well as bezafibrate significantly induced FGF21 mRNA expression in cultured mouse hepatocytes. On the other hand, both rosiglitazone and pioglitazone significantly induced, whereas bezafibrate did not affect FGF21 mRNA expression in the human liver carcinoma cell line HepG2. Bezafibrate significantly induced pyruvate dehydrogenase kinase 4 mRNA expression, suggesting that HepG2 cells are sensitive to bezafibrate like the mouse liver. Our findings suggest that PPARγ-activating antidiabetic drugs such as rosiglitazone and pioglitazone induce FGF21 expression in mouse and human hepatocytes, and that PPARγ rather than PPARα might play an important role in human FGF21 production.
关键词：fibroblast growth factor 21;rosiglitazone;pioglitazone;bezafibrate;HepG2;mouse liver