Graphical Abstract.

High-fat diet feeding in Ldlr-/-. Leiden mice induces obesity and associated metabolic dysfunction in adipose tissue (hypertrophy and inflammation), gut (increased permeability) and liver (non-alcoholic steatohepatitis; NASH). This NASH development in the liver is characterised by steatosis with disturbed cholesterol homeostasis and an associated inflammatory response, i.e. the infiltration of immune cells such as macrophages and neutrophils. Treatment with the multicomponent medicinal product HC-24 reduces hepatic accumulation of the cytotoxic lipid species free cholesterol and has anti-inflammatory effects in the liver – specifically reducing the infiltration of neutrophils into this tissue.