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| 1 | Dietary advanced glycation end-products aggravate non-alcoholic fatty liver disease显示文摘AIM To determine if manipulation of dietary advanced glycation end product(AGE), intake affects nonalcoholic fatty liver disease(NAFLD) progression and whether these effects are mediated via RAGE. METHODS Male C57Bl6 mice were fed a high fat, high fructose, high cholesterol(HFHC) diet for 33 wk and compared with animals on normal chow. A third group were given a HFHC diet that was high in AGEs. Another group was given a HFHC diet that was marinated in vinegar to prevent the formation of AGEs. In a second experiment, RAGE KO animals were fed a HFHC diet or a high AGE HFHC diet and compared with wildtype controls. Hepatic biochemistry, histology, picrosirius red morphometry and hepatic mR NA were determined. RESULTS Long-term consumption of the HFHC diet generated significant steatohepatitis and fibrosis after 33 wk. In this model, hepatic 4-hydroxynonenal content(a marker of chronic oxidative stress), hepatocyte ballooning, picrosirius red staining, α-smooth muscle actin and collagen type 1A gene expression were all significantly increased. Increasing the AGE content of the HFHC diet by baking further increased these markers of liver damage, but this was abrogated by pre-marination in acetic acid. In response to the HFHC diet, RAGE-/-animals developed NASH of similar severity to RAGE+/+ animals but were protected from the additional harmful effects of the high AGE containing diet. Studies in isolated Kupffer cells showed that AGEs increase cell proliferation and oxidative stress, providing a likely mechanism through which these compounds contribute to liver injury. CONCLUSION In the HFHC model of NAFLD, manipulation of dietary AGEs modulates liver injury, inflammation, and liver fibrosis via a RAGE dependent pathway. This suggests that pharmacological and dietary strategies targeting the AGE/RAGE pathway could slow the progression of NAFLD. | Christopher Leung Chandana B Herath Zhiyuan Jia Sof Andrikopoulos Bronwyn E Brown Michael J Davies Leni R Rivera John B Furness Josephine M Forbes Peter W Angus | 2016 | World Journal of Gastroenterology2016，22，35： | 7 |
| 2 | The enteric nervous system and regulation of intestinal motility 显示文摘 | Kunze W A Furness J B | 1999 | Annu Rev Physiol1999，61，： | 1 |
| 3 | The sites of action of 5-hydroxytryptamine in nerve-muscle preparations from the guinea-pig small intestine colon显示文摘 | COSTA M FURNESS J B | 1979 | Br J Pharmacol1979，65，： | 1 |
| 4 | Giardiasis surveillance -United States,1992-1997显示文摘 | Furness B W Beach M J Roberts J M | 2000 | Morbidity and Mortality Weekly Report CDC Surveillance Summary2000，49，： | 1 |
| 5 | Analysis of purinergic and cholinergic fast synaptic transmission to identified myenteric neurons显示文摘 | Nurgali K Furness J B Stebbing M J | 2003 | Neuroscience2003，116，： | 1 |
| 6 | Lobectomy performed through a video-assisted minithoracotomy as a new technique in our clinical practice显示文摘 | Furák J Bács E Grochulski R | 2008 | Magy Seb2008，61，1： | 1 |
| 7 | Security mechanisms analysis for ZigBee standard based on AES-CCM*显示文摘 | YANG B FUR Y DIAO J Z | 2012 | Advanced Materials Research2012，，468： | 1 |
| 8 | The enteric nervous system and regulation of intestinal motility显示文摘 | Kunze W A Furness J B | 1999 | Annu Rev Physiol1999，61，： | 1 |
| 9 | Nitric oxide syjnthase in the enteric nervous system of the guinea-pig:aquantitative description显示文摘 | FURNESS J B LI Z S YOUNG H M | 1994 | Cell Tissue Res1994，277，： | 1 |
| 10 | Intrinsic primary afferent neurons of the intestine显示文摘 | Furness J B Kunze W A Bertrand P P Clerc N Bornstein J C | 1998 | Prog Neurobiol1998，54，： | 1 |
| 11 | P2X2 purine receptor immunoreactivity of intraganglionic laminar endings in the mouse gastrointestinal tract 显示文摘 | Castelucci P Robbins H L Furness J B | 2003 | Cell Tissue Res2003，312，： | 1 |
| 12 | Nitric oxide synthase in the enteric nervous system of the guinea pig: a quantitative description 显示文摘 | Furness J B Li Z S Young H M | 1994 | Cell Tissue Res1994，277，： | 1 |
| 13 | The distribution of P2X3 purine receptor subunits in the guinea pig enteric nervous system显示文摘 | Poole D P Castelucci P Robbins H L Chiocchetti R Furness J B | 2002 | Auton Neurosci2002，101，12： | 1 |
| 14 | Total numbers of neurons in myenteric ganglia of the guinea- pig small intestine显示文摘 | Yong H M Furness J B Sewell P | 1993 | Cell Tissue Res1993，272，1： | 1 |
| 15 | Types of neurons in the enteric nervous system 显示文摘 | Furness J B | 2000 | J Auton Nerv Syst2000，81，： | 1 |
| 16 | Types of neurons in the enteric nervous system 显示文摘 | Furness J B | 2000 | J Auton Nerv Syst2000，81，13： | 1 |
| 17 | Nitric oxide synthase in neurons of the gastrointestinal tract of an avian species, Coturnix coturnix显示文摘 | Li Z S Young H M Furness J B | 1994 | J Anat1994，184，： | 1 |
| 18 | Giardiasis sur- veillance - United States, 1992 - 1997 显示文摘 | FURNESS B W BEACH M J ROBERTS J M | 2000 | Morbidity and Mor- tality Weekly Report CDC Surveillance Summary2000，49，7： | 1 |
| 19 | Origins of peptide and norepinephrine nerves in the mucosa of the guinea-pig small intestine显示文摘 | Kease J R Furness J B Costa M | 1984 | Gastroenterology1984，86，4： | 1 |
| 20 | Nitric oxide synthase in the enteric nervous system of the guinea- pig aquantitive description显示文摘 | Furness J B Li Z S Yong H M | 1994 | Cell Tissue Res1994，277，1： | 1 |
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