Treatment of NASH in mice with antidiabetic drugs

Einleitung:

The prevalence of non-alcoholic steatohepatitis (NASH) is continuously increasing worldwide. The pathogenesis of NASH is associated with type 2 diabetes and insulin resistance. Since there are still no specific drugs for NASH treatment, we have tested various antidiabetic drugs for NASH in mice.

Methoden:

Male C57Bl/6J mice received a Western diet (WD, 43% kcal from fat) enriched with 0.75% cholesterol for 24 weeks. Mice were kept on the diet and received once daily pioglitazone (25 mg/kg, p.o.), liraglutide (0.4 mg/kg, s.c.), empagliflozine (10 mg/kg, p.o.) or a combination of liraglutide and empagliflozine for eight weeks. The development of body composition and liver fat (computer tomography) was observed. Treatment outcome was evaluated by liver histology, biochemical analysis of liver tissue and plasma, and gene expression measurements.

Ergebnisse:

Feeding of WD induced trademarks of NASH (steatosis, inflammation, fibrosis) as well as obesity and insulin resistance. The level of transaminases (ALAT/ASAT) as a sign of liver damage was reduced by all treatments except Empagliflozin. Liraglutide improved steatosis and expression of inflammatory and fibrosis-related genes. The positive effects of liraglutide were partially reduced in combination with empagliflozin.

Schlussfolgerung:

Liraglutide was more efficient than other drugs to improve the pathogenesis of NASH by reducing steatosis and liver damage in mice.