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Am J Physiol Gastrointest Liver Physiol 293: G204-G210, 2007. First published March 29, 2007; doi:10.1152/ajpgi.00021.2007
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LIVER AND BILIARY TRACT

HGF ameliorates a high-fat diet-induced fatty liver

Takashi Kosone, Hitoshi Takagi, Norio Horiguchi, Yasuyo Ariyama, Toshiyuki Otsuka, Naondo Sohara, Satoru Kakizaki, Ken Sato, and Masatomo Mori

Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan

Submitted 9 January 2007 ; accepted in final form 26 March 2007

Hepatocyte growth factor (HGF) has various effects especially on epithelial cells. However, the precise role of HGF on lipogenesis is still not fully understood. A high-fat diet was administered to HGF transgenic mice and wild-type control mice in vivo. Furthermore, recombinant human HGF (rhHGF) was administered to HepG2 cell line in vitro. We performed an analysis regarding the factors relating to lipid metabolism. An overexpression of HGF dramatically ameliorates a high-fat diet-induced fatty liver. HGF transgenic mice showed an apparently reduced lipid accumulation in the liver. The activation of microsomal triglyceride transfer protein (MTP) and apolipoprotein B (ApoB) accompanying higher triglyceride levels in the serum were found in HGF transgenic mice on a normal diet. Interestingly, this upregulation of the MTP activation became more apparent in the high-fat diet. In addition, the administration of rhHGF stimulated MTP and ApoB expression while reducing reduced the intracellular lipid content in HepG2 cell line. However, this induction of MTP and ApoB by HGF was clearly inhibited by PD98059 (MAPK inhibitor). In conclusion, the data presented in this study indicated that HGF ameliorates a high-fat diet-induced fatty liver via the activation of MTP and ApoB.

hepatocyte growth factor; fatty liver; microsomal triglyceride transfer protein; apolipoprotein B


Address for reprint requests and other correspondence: H. Takagi, Dept. of Medicine and Molecular Science, Gunma Univ. Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma 371-8511, Japan (e-mail: htakagi{at}med.gunma-u.ac.jp)




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