Rat Strain Differences in Susceptibility to Alcohol-Induced Chronic Liver Injury and Hepatic Insulin Resistance
The finding of more severe steatohepatitis in alcohol fed Long Evans (LE) compared with Sprague Dawley (SD) and Fisher 344 (FS) rats prompted us to determine whether host factors related to alcohol metabolism, inflammation, and insulin/IGF signaling predict proneness to alcohol-mediated liver injury...
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| Format: | Article |
| Language: | English |
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Wiley
2010-01-01
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| Series: | Gastroenterology Research and Practice |
| Online Access: | http://dx.doi.org/10.1155/2010/312790 |
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| author | Sarah M. DeNucci Ming Tong Lisa Longato Margot Lawton Mashiko Setshedi Rolf I. Carlson Jack R. Wands Suzanne M. de la Monte |
| author_facet | Sarah M. DeNucci Ming Tong Lisa Longato Margot Lawton Mashiko Setshedi Rolf I. Carlson Jack R. Wands Suzanne M. de la Monte |
| author_sort | Sarah M. DeNucci |
| collection | DOAJ |
| description | The finding of more severe steatohepatitis in alcohol fed Long Evans (LE) compared with Sprague Dawley (SD) and Fisher 344 (FS) rats prompted us to determine whether host factors related to alcohol metabolism, inflammation, and insulin/IGF signaling predict proneness to alcohol-mediated liver injury. Adult FS, SD, and LE rats were fed liquid diets containing 0% or 37% (calories) ethanol for 8 weeks. Among controls, LE rats had significantly higher ALT and reduced GAPDH relative to SD and FS rats. Among ethanol-fed rats, despite similar blood alcohol levels, LE rats had more pronounced steatohepatitis and fibrosis, higher levels of ALT, DNA damage, pro-inflammatory cytokines, ADH, ALDH, catalase, GFAP, desmin, and collagen expression, and reduced insulin receptor binding relative to FS rats. Ethanol-exposed SD rats had intermediate degrees of steatohepatitis, increased ALT, ADH and profibrogenesis gene expression, and suppressed insulin receptor binding and GAPDH expression, while pro-inflammatory cytokines were similarly increased as in LE rats. Ethanol feeding in FS rats only reduced IL-6, ALDH1–3, CYP2E1, and GAPDH expression in liver. In conclusion, susceptibility to chronic steatohepatitis may be driven by factors related to efficiency of ethanol metabolism and degree to which ethanol exposure causes hepatic insulin resistance and cytokine activation. |
| format | Article |
| id | doaj-art-06123ee00d704a0ab44ed004aec96910 |
| institution | Kabale University |
| issn | 1687-6121 1687-630X |
| language | English |
| publishDate | 2010-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Gastroenterology Research and Practice |
| spelling | doaj-art-06123ee00d704a0ab44ed004aec969102025-02-03T01:23:42ZengWileyGastroenterology Research and Practice1687-61211687-630X2010-01-01201010.1155/2010/312790312790Rat Strain Differences in Susceptibility to Alcohol-Induced Chronic Liver Injury and Hepatic Insulin ResistanceSarah M. DeNucci0Ming Tong1Lisa Longato2Margot Lawton3Mashiko Setshedi4Rolf I. Carlson5Jack R. Wands6Suzanne M. de la Monte7Departments of Medicine and Pathology, Liver Research Center, Rhode Island Hospital and the Warren Alpert Medical School of Brown University, Pierre Galletti Research Building, 55 Claverick Street, Room 421, Providence, RI 02903, USADepartments of Medicine and Pathology, Liver Research Center, Rhode Island Hospital and the Warren Alpert Medical School of Brown University, Pierre Galletti Research Building, 55 Claverick Street, Room 421, Providence, RI 02903, USADepartments of Medicine and Pathology, Liver Research Center, Rhode Island Hospital and the Warren Alpert Medical School of Brown University, Pierre Galletti Research Building, 55 Claverick Street, Room 421, Providence, RI 02903, USADepartments of Medicine and Pathology, Liver Research Center, Rhode Island Hospital and the Warren Alpert Medical School of Brown University, Pierre Galletti Research Building, 55 Claverick Street, Room 421, Providence, RI 02903, USADepartments of Medicine and Pathology, Liver Research Center, Rhode Island Hospital and the Warren Alpert Medical School of Brown University, Pierre Galletti Research Building, 55 Claverick Street, Room 421, Providence, RI 02903, USADepartments of Medicine and Pathology, Liver Research Center, Rhode Island Hospital and the Warren Alpert Medical School of Brown University, Pierre Galletti Research Building, 55 Claverick Street, Room 421, Providence, RI 02903, USADepartments of Medicine and Pathology, Liver Research Center, Rhode Island Hospital and the Warren Alpert Medical School of Brown University, Pierre Galletti Research Building, 55 Claverick Street, Room 421, Providence, RI 02903, USADepartments of Medicine and Pathology, Liver Research Center, Rhode Island Hospital and the Warren Alpert Medical School of Brown University, Pierre Galletti Research Building, 55 Claverick Street, Room 421, Providence, RI 02903, USAThe finding of more severe steatohepatitis in alcohol fed Long Evans (LE) compared with Sprague Dawley (SD) and Fisher 344 (FS) rats prompted us to determine whether host factors related to alcohol metabolism, inflammation, and insulin/IGF signaling predict proneness to alcohol-mediated liver injury. Adult FS, SD, and LE rats were fed liquid diets containing 0% or 37% (calories) ethanol for 8 weeks. Among controls, LE rats had significantly higher ALT and reduced GAPDH relative to SD and FS rats. Among ethanol-fed rats, despite similar blood alcohol levels, LE rats had more pronounced steatohepatitis and fibrosis, higher levels of ALT, DNA damage, pro-inflammatory cytokines, ADH, ALDH, catalase, GFAP, desmin, and collagen expression, and reduced insulin receptor binding relative to FS rats. Ethanol-exposed SD rats had intermediate degrees of steatohepatitis, increased ALT, ADH and profibrogenesis gene expression, and suppressed insulin receptor binding and GAPDH expression, while pro-inflammatory cytokines were similarly increased as in LE rats. Ethanol feeding in FS rats only reduced IL-6, ALDH1–3, CYP2E1, and GAPDH expression in liver. In conclusion, susceptibility to chronic steatohepatitis may be driven by factors related to efficiency of ethanol metabolism and degree to which ethanol exposure causes hepatic insulin resistance and cytokine activation.http://dx.doi.org/10.1155/2010/312790 |
| spellingShingle | Sarah M. DeNucci Ming Tong Lisa Longato Margot Lawton Mashiko Setshedi Rolf I. Carlson Jack R. Wands Suzanne M. de la Monte Rat Strain Differences in Susceptibility to Alcohol-Induced Chronic Liver Injury and Hepatic Insulin Resistance Gastroenterology Research and Practice |
| title | Rat Strain Differences in Susceptibility to Alcohol-Induced Chronic Liver Injury and Hepatic Insulin Resistance |
| title_full | Rat Strain Differences in Susceptibility to Alcohol-Induced Chronic Liver Injury and Hepatic Insulin Resistance |
| title_fullStr | Rat Strain Differences in Susceptibility to Alcohol-Induced Chronic Liver Injury and Hepatic Insulin Resistance |
| title_full_unstemmed | Rat Strain Differences in Susceptibility to Alcohol-Induced Chronic Liver Injury and Hepatic Insulin Resistance |
| title_short | Rat Strain Differences in Susceptibility to Alcohol-Induced Chronic Liver Injury and Hepatic Insulin Resistance |
| title_sort | rat strain differences in susceptibility to alcohol induced chronic liver injury and hepatic insulin resistance |
| url | http://dx.doi.org/10.1155/2010/312790 |
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