Gender-related differences in response to DUAL diet in murine model of steatohepatitis

Background and Aims Chronic alcohol intake is an important risk factor for Metabolic Associated Fatty Liver Disease (MAFLD) progression. However, the patients with dual clinical features of MAFLD and ALD (alcohol-associated liver disease) represent a large, understudied area in hepatology with a huge unmet need in preclinical and clinical studies. In the present study we evaluated and compared the extent of liver damage, steatosis, inflammation, and fibrosis in DUAL murine model with main focus on gender related differences.

Methods 10 weeks old C57BL6/J male and female mice were treated with DUAL diet (WD with sweetened drinking water and 10% alcohol) for 23 weeks. Mice receiving standard chow diet and tap water were used as control. Serum markers of liver damage, immunohistochemistry (IHC), immunofluorescence (IF), histopathology and gene expression were analyzed.

Results Feeding with DUAL diet caused significantly faster and stronger weight gain in male mice compared to females. Male rodent displayed more prominent obesity, hypercholesterolemia and elevated plasma levels of AST, ALT, LDH. The liver of male mice was characterized by more significant liver damage and more prominent hepatomegaly, profound liver steatosis and positive TUNEL staining. DUAL feeding in male mice resulted in significant lobular inflammation. Notably, DUAL male mice exhibited stronger collagen accumulation and more progressive hepatic fibrosis compared to females. Conclusions Our study confirmed that the gender differences in patients with DUAL chronic liver diseases (MAFLD + ALD) have to be taken under consideration for clinical practice to improve diagnostic and therapeutical approaches in the future.

Publication History

Article published online:
26 January 2022