Motomura Wataru, Inoue Mitsutaka, Ohtake Takaaki, Takahashi Nubuhiko, Nagamine Miho, Tanno Satoshi, Kohgo Yutaka, Okumura Toshikatsu
Third Department of Internal Medicine, Asahikawa Medical College, Asahikawa, Japan.
Biochem Biophys Res Commun. 2006 Feb 24;340(4):1111-8. doi: 10.1016/j.bbrc.2005.12.121. Epub 2005 Dec 28.
The present study was performed to examine a role of adipose differentiation-related protein (ADRP) in the process of liver steatosis. Immunohistochemical findings indicated that ADRP expression is increased in the hepatocytes in patients with fatty liver when compared with normal liver. ADRP expression is localized in the surface of lipid droplets in the hepatocytes. Increased expression of ADRP mRNA and protein was similarly observed in fatty liver in ob/ob mice and the liver steatosis induced by high fat diet in mice. The up-regulation of ADRP mRNA and protein in the liver by high fat diet was identified in the surface of lipid droplets in a time-dependent manner. Recent studies demonstrated that up-regulation of PPARgamma in the hepatocytes is deeply involved in liver steatosis. To clarify whether ADRP expression is increased by PPARgamma activation in hepatocytes, we examined the effect of a PPARgamma ligand, troglitazone, on ADRP mRNA expression in HepG2 cells. ADRP mRNA expression was increased by troglitazone in dose- and time-dependent manners. All these results suggest that ADRP is up-regulated in liver steatosis in human and mice, and that high fat diet increases expression of ADRP through PPARgamma activation, followed by induction of liver steatosis.
本研究旨在探讨脂肪分化相关蛋白（ADRP）在肝脏脂肪变性过程中的作用。免疫组化结果表明，与正常肝脏相比，脂肪肝患者肝细胞中ADRP表达增加。ADRP表达定位于肝细胞内脂滴表面。在ob/ob小鼠的脂肪肝以及小鼠高脂饮食诱导的肝脏脂肪变性中，同样观察到ADRP mRNA和蛋白表达增加。高脂饮食对肝脏中ADRP mRNA和蛋白的上调在脂滴表面呈时间依赖性。最近的研究表明，肝细胞中PPARγ的上调与肝脏脂肪变性密切相关。为了阐明ADRP表达是否通过肝细胞中PPARγ的激活而增加，我们检测了PPARγ配体曲格列酮对HepG2细胞中ADRP mRNA表达的影响。曲格列酮以剂量和时间依赖性方式增加ADRP mRNA表达。所有这些结果表明，ADRP在人和小鼠的肝脏脂肪变性中上调，高脂饮食通过激活PPARγ增加ADRP表达，进而诱导肝脏脂肪变性。
