Fat and carbohydrate in western diet contribute differently to hepatic lipid accumulation

•Western diet-fed ChREBP knockout mice exhibit hepatic lipid accumulation.•β-oxidation and VLDL secretion are decreased in ChREBP knockout mice.•Intestinal lipid absorption is increased in ChREBP knockout mice.•Inflammation and fibrosis are lower in ChREBP knockout mice.•Dietary fat and dietary carbohydrate promote hepatic steatosis differently.

We investigated the contributions of dietary fat and dietary carbohydrate to the development of fatty liver induced by western diet (WD). Compared with WD-fed wild type (WT) mice, livers of WD-fed ChREBP−/− mice showed lipid droplets of varying sizes around the hepatic lobules, while hepatic triglyceride and cholesterol contents were only modestly decreased. Inflammation and fibrosis were suppressed in ChREBP−/− mice. In addition, compared with WD-fed WT mice, ChREBP−/− mice showed decreased β-oxidation, ketogenesis and FGF21 production, increased intestinal lipid absorption, and decreased VLDL secretion. These findings suggest that dietary fat and carbohydrate contribute differently to the development of fatty liver.