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| 1 | Lack of hepcidin expression attenuates steatosis and causesfibrosis in the liver显示文摘AIM: To investigate the role of key iron-regulatory protein, hepcidin in non-alcoholic fatty liver disease(NAFLD). METHODS: Hepcidin(Hamp1) knockout and floxed control mice were administered a high fat and high sucrose(HFS) or a regular control diet for 3 or 7 mo. Steatosis, triglycerides, fibrosis, protein and gene expression in mice livers were determined by histological and biochemical techniques, western blotting and realtime polymerase chain reaction. RESULTS: Knockout mice exhibited hepatic iron accumulation. Despite similar weight gains, HFS feeding induced hepatomegaly in floxed, but not knockout, mice. The livers of floxed mice exhibited higher levels of steatosis, triglycerides and c-Jun N-terminal kinase(JNK) phosphorylation than knockout mice. In contrast, a significant increase in fibrosis was observed in knockout mice livers within 3 mo of HFS administration. The hepatic gene expression levels of sterol regulatoryelement-binding protein-1c and fat-specific protein-27, but not peroxisome proliferator-activated receptoralpha or microsomal triglyceride transfer protein, were attenuated in HFS-fed knockout mice. Knockout mice fed with regular diet displayed increased carnitine palmitoyltransferase-1a and phosphoenolpyruvate carboxykinase-1 but decreased glucose-6-phosphatase expression in the liver. In summary, attenuated steatosis correlated with decreased expression of lipogenic and lipid storage genes, and JNK phosphorylation. Deletion of Hamp1 alleles per se modulated hepatic expression of beta-oxidation and gluconeogenic genes. CONCLUSION: Lack of hepcidin expression inhibits hepatic lipid accumulation and induces early development of fibrosis following high fat intake. Hepcidin and iron may play a role in the regulation of metabolic pathways in the liver, which has implications for NAFLD pathogenesis. | Sizhao Lu Robert G Bennett Kusum K Kharbanda Duygu Dee Harrison-Findik | 2016 | World Journal of Hepatology2016，8，4： | 3 |
| 2 | Serelaxin increases the antifibrotic action of rosiglitazone in a model of hepatic fibrosis显示文摘AIM To determine the effect of combined serelaxin and rosiglitazone treatment on established hepatic fibrosis.METHODS Hepatic fibrosis was induced in mice by carbon tetrachloride administration for 6 wk, or vehicle alone(nonfibrotic mice). For the final 2 wk, mice were treated with rosiglitazone, serelaxin, or both rosiglitazone and serelaxin. Serum liver enzymes and relaxin levels were determined by standard methods. The degree of liver collagen content was determined by histology and immunohistochemistry. Expression of type?Ⅰ?collagen was determined by quantitative PCR. Activation of hepatic stellate cells was assessed by alpha-smoothmuscle actin(SMA) levels. Liver peroxisome proliferator activated receptor-gamma coactivator 1 alpha(PGC1α) was determined by Western blotting.RESULTS Treatment of mice with CCl4 resulted in hepatic fibrosis as evidenced by increased liver enzyme levels(ALT and AST), and increased liver collagen and SMA. Monotherapy with either serelaxin or rosiglitazone for 2 wk was generally without effect. In contrast, the combination of serelaxin and rosiglitazone resulted in significantly improved ALT levels(P < 0.05). Total liver collagen content as determined by Sirius red staining revealed that only combination treatment was effective in reducing total liver collagen(P < 0.05). These results were supported by immunohistochemistry for type?Ⅰ?collagen, in which only combination treatment reduced fibrillar collagen levels(P < 0.05). The level of hepatic stellate cell activation was modestly, but significantly, reduced by serelaxin treatment alone, but combination treatment resulted in significantly lower SMA levels. Finally, while hepatic fibrosis reduced liver PGC1α levels, the combination of serelaxin and rosiglitazone resulted in restoration of PGC1α protein levels.CONCLUSION The combination of serelaxin and rosiglitazone treatment for 2 wk was effective in significantly reducing established hepatic fibrosis, providing a potential new treatment strategy. | Robert G Bennett Ronda L Simpson Frederick G Hamel | 2017 | World Journal of Gastroenterology2017，23，22： | 2 |
| 3 | Privacy Amplification by Public Discussion显示文摘 | Bennett C H Brassard G Robert J M | 1988 | SIAM Journal on Computing1988，17，02： | 1 |
| 4 | Privacy Amplification by Public Discussion显示文摘 | Bennett C H Brassard G Robert J M | 1988 | SIAN Journal on Computing1988，17，2： | 1 |
| 5 | Privacy amplification by public discussion显示文摘 | Bennett C H Brassard G Robert J M | 1988 | SIAM Journal on Computing1988，17，2： | 1 |
| 6 | Privacy amplification by public discussion显示文摘 | Bennett C H Brassard G Robert J M | 1988 | SIAM J on Computing1988，17，2： | 1 |
| 7 | Privacy amplification by public discussion显示文摘 | Bennett C H Brassard G Robert J M | 1988 | SIAM Journal on Computing1988，17，2： | 1 |
| 8 | Privacy Amplification by Public Discussion显示文摘 | Bennett C H Brassard G Robert J M | 1988 | SIAN Journal on Computing1988，17，2： | 1 |
| 9 | Privacy Amplification by Public Discussion显示文摘 | Bennett C H Brassard G Robert J M | 1988 | SIAN Journal on Computing1988，17，2： | 1 |
| 10 | Efficacy of a subsurface-flow wetland using the estuarine sedge Juncus kraussii to treat effluent from inland saline aquaculture显示文摘 | Lymbery A J Doupé Robert G Bennett T Starcevich MR | 2006 | Aquacultural Engineering2006，34，1： | 1 |
| 11 | Privacy amplification by public discussion显示文摘 | BENNETT C BRASSARD G ROBERT J | 1988 | SIAM J Comput1988，17，2： | 1 |
| 12 | Privacy Amplification by Public Discussion显示文摘 | Bennett C H Brassard G Robert J M | 1988 | SIAM J Computing1988，17，2： | 1 |
| 13 | An implicit finite element material model for energetic particulate composite ma- terials显示文摘 | Robert M H Bennett G | 2000 | International Journal for Numerical Methods in Engineering2000，49，9： | 1 |
| 14 | An Implicit Finite Element Material Model for Energetic Particulate Composite Materials 显示文摘 | Robert M Hackett Joel G Bennett | 2000 | International Journal for Numerical Methods in Engineering2000，49，9： | 1 |
| 15 | Privacy Amplification by Public Discussion 显示文摘 | BENNETT C H BRASSARD G ROBERT J-M | 1988 | SIAM J Comput1988，17，2： | 1 |
| 16 | Efficiency of a subsurface-flow wetland using the estuarine sedge Juncus kraussii to treat effluent from inland saline aquaculture显示文摘 | Alan J Lymbery Robert G Doupé Thomas Bennett | | 0，，01： | 1 |
| 17 | Privacy Amplification by Public Discussion显示文摘 | BENNETT C H BRASSARD G ROBERT J | | 0，，： | 1 |
| 18 | Biological activity of a fragment of insulin显示文摘 | William C Duckworth Janet Fawcett Brian T Tsui Robert G Bennett Frederick G Hamel | 2004 | Biochemical and Biophysical Research Communications2004，，4： | 1 |
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