Disruption of HSD17B12 in mouse hepatocytes leads to reduce body weight and defect in the lipid droplet expansion associated with microvesicular steatosis

Hepatocyte-specific knockout mice of Hydroxysteroid dehydrogenase 12 (LiB12cKO) show significant fat accumulation in their liver. As they age, they also show a reduced whole-body fat percentage. However, liver fat accumulation does not result in the typical formation of large lipid droplets; instead, small droplets were more prevalent in the LiB12cKO liver. This indicates a failure in the lipid droplet (LD) expansion. This was associated with liver damage, presumably due to lipotoxicity. The increase in the CIDEC expression further supported the deficiency in LD expansion in the LiB12cKO liver, and the downregulation of several members of the MUP family of proteins suggests the presence of endoplasmic reticulum stress LiB12cKO liver.