| Summary: | 碩士 === 國立中山大學 === 生物科學系研究所 === 106 === Hepatoma-derived growth factor (HDGF), a nuclear oncoprotein highly expressed in both fetal hepatocytes and hepatoma tissues, has been previously demonstrated to play a profibrogenic role in hepatic fibrogenesis through aggravating TGF-1 signaling. This study examined the role of HDGF in the development of non-alcoholic fatty liver disease (NAFLD).
In this study, adult male C57BL/6 mice were fed with high fat diet for 4 wk and subsequent choline-deficient diet (CDD) for 8 wks to induce NAFLD. Sera and liver tissues were subjected to biochemical, histopathological, and molecular examinations. Adenoviral-mediated HDGF over-expression or knockdown was used to evaluate its possible prophylactic effect.
Elevation of total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C), and low density lipoprotein-cholesterol (LDL-C) in mouse sera confirmed the successfulness of NAFLD induction. Histologically, oil red O staining data showed a typical pattern of fatty droplet deposition in liver tissues. Quantitative PCR and Western blotting detection indicated that HDGF, TGF-1, COL1A1, and PPAR- were up-regulated in steatotic livers after 6 weeks of CDD feeding. Adenovirus-mediated HDGF gene overexpression did not affect AST, ALT, and TG serum levels in NAFLD mice. Conversely, HDGF siRNA delivery significantly suppressed TC level. Oil red staining and morphometric analysis revealed that both HDGF over-expression and gene silencing suppressed the spreading area of and the averaged size of the fatty droplets deposited in NAFLD livers, suggesting that HDGF might play a role in fatty acid synthesis and/or transportation, thereby ameliorating fatty liver retention in livers.
These findings suggest that HDGF is functionally involved in lipogenesis of liver metabolism and that HDGF modifications ameliorate fatty acid deposition during NAFLD development. Accordingly, HDGF gene modifications may be regarded a therapeutic modality for NAFLD treatment.
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