Sex- and hepatocyte Pparg-dependent hepatic effects of a high fat diet containing 60% kcal from fat and 2% cholesterol, which was supplemented with 10% fructose in the drinking water (HFC+Fr) to induce diet-induced obesity in male and female mice.

Most western diets or Amilyn-based diets induce MASLD and MASH in mice but do not fully reproduce metabolic dysfunction in male and female mice. In this study, a high fat diet containing cholesterol (D12120101, Research Diets, Inc) supplemented with 10% w/v fructose in the drinking water (HFC+Fr diet) was provided to control and hepatocyte specific Pparg knockout male and female mice for 24 weeks. Both HFC+Fr-fed male and female mice developed obesity and insulin resistance. Only male mice developed clear signs of MASH with fibrosis. Hepatocyte specific Pparg had a significant effect in the regulation of hepatic transcriptomics in HFC+Fr-fed male mice.