scholarly journals Differences in metabolic and liver pathobiology induced by two dietary mouse models of nonalcoholic fatty liver disease

2020 ◽  
Author(s):  
Hannah Zhang ◽  
Mélissa Léveillé ◽  
Emilie Courty ◽  
Aysim Gunes ◽  
Bich Nguyen ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Liver Disease ◽  
Liver Cancer ◽  
Fatty Liver ◽  
Liver Damage ◽  
Fatty Liver Disease ◽  
Western Diet ◽  
Chow Diet ◽  
Alcoholic Fatty Liver ◽  
Obesity And Diabetes

ABSTRACTNon-alcoholic fatty liver disease (NAFLD) is a growing epidemic associated with key aspects of metabolic disease such as obesity and diabetes. The first stage of NAFLD is characterized by lipid accumulation in hepatocytes, but this can further progress into non-alcoholic steatohepatitis (NASH), fibrosis or cirrhosis, and hepatocellular carcinoma (HCC). A western diet, high in fats, sugars and cholesterol is linked to NAFLD development. Murine models are often used to experimentally study NAFLD, as they can display similar histopathological features as humans; however, there remains debate on which diet-induced model most appropriately and consistently 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), comparing them to a common grain-based chow diet (GBD). Mice on both experimental diets developed liver steatosis, while 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 tumour burdens in a model of diet-potentiated liver cancer. Response to diet and resulting phenotypes were generally similar between sexes, albeit delayed in females. Notably, although metabolic and liver disease phenotypes are often thought to progress in parallel, 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 are reliable methods 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.

scholarly journals Differences in metabolic and liver pathobiology induced by two dietary mouse models of nonalcoholic fatty liver disease

2020 ◽  
Vol 319 (5) ◽  
pp. E863-E876
Author(s):  
Hannah Zhang ◽  
Mélissa Léveillé ◽  
Emilie Courty ◽  
Aysim Gunes ◽  
Bich N. Nguyen ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Liver Disease ◽  
Liver Cancer ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Liver Damage ◽  
Fatty Liver Disease ◽  
Liver Steatosis ◽  
Chow Diet ◽  
Nonalcoholic Fatty Liver

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.

scholarly journals Mechanisms of Non-Alcoholic Fatty Liver Disease in the Metabolic Syndrome. A Narrative Review

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 270
Author(s):  
Luca Rinaldi ◽  
Pia Clara Pafundi ◽  
Raffaele Galiero ◽  
Alfredo Caturano ◽  
Maria Vittoria Morone ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Risk Factor ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Smoking Habit ◽  
Lifestyle Modifications ◽  
Alcoholic Fatty Liver ◽  
The Metabolic Syndrome ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) are two different entities sharing common clinical and physio-pathological features, with insulin resistance (IR) as the most relevant. Large evidence leads to consider it as a risk factor for cardiovascular disease, regardless of age, sex, smoking habit, cholesterolemia, and other elements of MS. Therapeutic strategies remain still unclear, but lifestyle modifications (diet, physical exercise, and weight loss) determine an improvement in IR, MS, and both clinical and histologic liver picture. NAFLD and IR are bidirectionally correlated and, consequently, the development of pre-diabetes and diabetes is the most direct consequence at the extrahepatic level. In turn, type 2 diabetes is a well-known risk factor for multiorgan damage, including an involvement of cardiovascular system, kidney and peripheral nervous system. The increased MS incidence worldwide, above all due to changes in diet and lifestyle, is associated with an equally significant increase in NAFLD, with a subsequent rise in both morbidity and mortality due to both metabolic, hepatic and cardiovascular diseases. Therefore, the slowdown in the increase of the “bad company” constituted by MS and NAFLD, with all the consequent direct and indirect costs, represents one of the main challenges for the National Health Systems.

scholarly journals Non-alcoholic fatty liver disease: the hepatic consequence of obesity and the metabolic syndrome

2010 ◽  
Vol 69 (2) ◽  
pp. 211-220 ◽  
Author(s):  
J. Bernadette Moore
Keyword(s):  
Metabolic Syndrome ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Response To Treatment ◽  
Health Concern ◽  
Alcoholic Fatty Liver ◽  
The Metabolic Syndrome ◽  
Increased Risk ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is now the most common liver disease in both adults and children worldwide. As a disease spectrum, NAFLD may progress from simple steatosis to steatohepatitis, advanced fibrosis and cirrhosis. An estimated 20–35% of the general population has steatosis, 10% of whom will develop the more progressive non-alcoholic steatohepatitis associated with markedly increased risk of cardiovascular- and liver-related mortality. Development of NAFLD is strongly linked to components of the metabolic syndrome including obesity, insulin resistance, dyslipidaemia and type 2 diabetes. The recognition that NAFLD is an independent risk factor for CVD is a major public health concern. There is a great need for a sensitive non-invasive test for the early detection and assessment of the stage of NAFLD that could also be used to monitor response to treatment. The cellular and molecular aetiology of NAFLD is multi-factorial; genetic polymorphisms influencing NAFLD have been identified and nutrition is a modifiable environmental factor influencing NAFLD progression. Weight loss through diet and exercise is the primary recommendation in the clinical management of NAFLD. The application of systems biology to the identification of NAFLD biomarkers and factors involved in NAFLD progression is an area of promising research.

Sign in / Sign up

Export Citation Format

Share Document