Article ; Online: Differences in metabolic and liver pathobiology induced by two dietary mouse models of nonalcoholic fatty liver disease.
American journal of physiology. Endocrinology and metabolism
2020 Volume 319, Issue 5, Page(s) E863–E876
Abstract: Nonalcoholic fatty liver disease (NAFLD) is a growing epidemic linked to metabolic disease. The first stage of NAFLD is characterized by lipid accumulation in hepatocytes, but this can progress into nonalcoholic steatohepatitis (NASH), cirrhosis, and ... ...
| Abstract | Nonalcoholic fatty liver disease (NAFLD) is a growing epidemic linked to metabolic disease. The first stage of NAFLD is characterized by lipid accumulation in hepatocytes, but this can progress into nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma (HCC). Western diets, high in fats, sugars, and cholesterol, are linked to NAFLD development. Murine models are often used to study NAFLD; however, there remains debate on which diet-induced model best mimics both human disease progression and pathogenesis. In this study, we performed a side-by-side comparison of two popular diet models of murine NAFLD/NASH and associated HCC, a high-fat diet supplemented with 30% fructose water (HFHF) and a Western diet high in cholesterol (WDHC), and these were compared with a common grain-based chow diet (GBD). Mice on both experimental diets developed liver steatosis, and WDHC-fed mice had greater levels of hepatic inflammation and fibrosis than HFHF-fed mice. In contrast, HFHF-fed mice were more obese and developed more severe metabolic syndrome, with less pronounced liver disease. Despite these differences, WDHC-fed and HFHF-fed mice had similar tumor burdens in a model of diet-potentiated liver cancer. Response to diet and resulting phenotypes were generally similar between sexes, albeit delayed in females. This study shows that modest differences in diet can significantly uncouple glucose homeostasis and liver damage. In conclusion, long-term feeding of either HFHF or WDHC is a reliable method to induce NASH and diet-potentiated liver cancer in mice of both sexes; however, the choice of diet involves a trade-off between severity of metabolic syndrome and liver damage. |
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| MeSH term(s) | Animals ; Carcinoma, Hepatocellular/etiology ; Carcinoma, Hepatocellular/metabolism ; Carcinoma, Hepatocellular/pathology ; Diet, High-Fat ; Diet, Western ; Disease Models, Animal ; Disease Progression ; Female ; Hepatocytes/metabolism ; Hepatocytes/pathology ; Lipid Metabolism/physiology ; Liver/metabolism ; Liver/pathology ; Liver Neoplasms/etiology ; Liver Neoplasms/metabolism ; Liver Neoplasms/pathology ; Male ; Mice ; Non-alcoholic Fatty Liver Disease/complications ; Non-alcoholic Fatty Liver Disease/metabolism ; Non-alcoholic Fatty Liver Disease/pathology |
| Language | English |
| Publishing date | 2020-09-14 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 603841-4 |
| ISSN | 1522-1555 ; 0193-1849 |
| ISSN (online) | 1522-1555 |
| ISSN | 0193-1849 |
| DOI | 10.1152/ajpendo.00321.2020 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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