Atorvastatin Attenuates Diet-Induced Non-Alcoholic Steatohepatitis in APOE*3-Leiden Mice by Reducing Hepatic Inflammation

Patients with metabolic syndrome are often prescribed statins to prevent the development of cardiovascular disease. Conversely, data on their effects on non-alcoholic steatohepatitis (NASH) are lacking. We evaluated these effects by feeding APOE*3-Leiden mice a Western-type diet (WTD) with or without atorvastatin to induce NASH and hepatic...

Semaglutide Has Beneficial Effects on Non-Alcoholic Steatohepatitis in Ldlr-/-.Leiden Mice

Semaglutide, a glucagon-like peptide-1 receptor agonist, is an antidiabetic medication that has recently been approved for the treatment of obesity as well. Semaglutide is postulated to be a promising candidate for the treatment of non-alcoholic steatohepatitis (NASH). Here, Ldlr-/-.Leiden mice received a fast-food diet (FFD) for 25 weeks,...

Beneficial effects of elafibranor on NASH in E3L.CETP mice and differences between mice and men

Non-alcoholic steatohepatitis (NASH) is the most rapidly growing liver disease that is nevertheless without approved pharmacological treatment. Despite great effort in developing novel NASH therapeutics, many have failed in clinical trials. This has raised questions on the adequacy of preclinical models. Elafibranor is one of the drugs currently...

Diet and exercise reduce pre-existing NASH and fibrosis and have additional beneficial effects on the vasculature, adipose tissue and skeletal muscle via organ-crosstalk

Background. Non-alcoholic steatohepatitis (NASH) has become one of the most common liver diseases and is still without approved pharmacotherapy. Lifestyle interventions using exercise and diet change remain the current treatment of choice and even a small weight loss (5–7%) can already have a beneficial effect on NASH. However, the underlying...

A Translational Mouse Model for NASH with Advanced Fibrosis and Atherosclerosis Expressing Key Pathways of Human Pathology

Non-alcoholic steatohepatitis (NASH) is a fast-growing liver disorder that is associated with an increased incidence of cardiovascular disease and type 2 diabetes. Animal models adequately mimicking this condition are scarce. We herein investigate whether Ldlr−/−. Leiden mice on different high-fat diets represent a suitable NASH model. Ldlr−/−....

The APOE∗3-Leiden Heterozygous Glucokinase Knockout Mouse as Novel Translational Disease Model for Type 2 Diabetes, Dyslipidemia, and Diabetic Atherosclerosis

Background. There is a lack of predictive preclinical animal models combining atherosclerosis and type 2 diabetes. APOE*3-Leiden (E3L) mice are a well-established model for diet-induced hyperlipidemia and atherosclerosis, and glucokinase+/− (GK+/−) mice are a translatable disease model for glucose control in type 2 diabetes. The respective mice...

Plasticity of lifelong calorie-restricted C57BL/6J mice in adapting to a medium-fat diet intervention at old age

Calorie restriction (CR) is a dietary regimen that supports healthy aging. In this study, we investigated the systemic and liver-specific responses caused by a diet switch to a medium-fat (MF) diet in 24-month-old lifelong, CR-exposed mice. This study aimed to increase the knowledge base on dietary alterations of gerontological relevance. Nine...

Metabolically induced liver inflammation leads to NASH and differs from LPS-or IL-1β-induced chronic inflammation

The nature of the chronic inflammatory component that drives the development of non-alcoholic steatohepatitis (NASH) is unclear and possible inflammatory triggers have not been investigated systematically. We examined the effect of non-metabolic triggers (lipopolysaccharide (LPS), interleukin-1β (IL-1β), administered by slow-release minipumps)...

Establishment of a general NAFLD scoring system for rodent models and comparison to human liver pathology

Results: The criteria macrovesicular steatosis, microvesicular steatosis, hepatocellular hypertrophy, inflammation and fibrosis were generally applicable to rodent NAFLD. The inter-observer reproducibility (evaluated using the Intraclass Correlation Coefficient) between the ten observers was high for the analysis of macrovesicular steatosis and...