Considering our recent finding that hepatic TG content is lower in IVA-PLA2-knockout mice fed normal chow diets than in wild-type mice, it is possible that a suppression of IVA-PLA2 protects against the development of fatty liver under HF dietary conditions. Taking this into account, in the present study, we examined the possible involvement of IVA-PLA2 in the development of fatty liver using IVA-PLA2-knockout mice fed HF diets. The current study demonstrated that a deficiency of IVA-PLA2 protected mice against HF diet-induced increases in the Sulfamonomethoxine number of hepatocytes exhibiting cytoplasmic vacuolation and hepatic TG content accompanying liver damage. These findings and further results shown here suggest that IVA-PLA2 is involved in the development of fatty liver damage under HF dietary conditions. Microscopic views of the liver of wild-type and IVA-PLA2knockout mice fed normal or HF diets for 8 or 16 weeks are shown in Figure 1. The results reveal an apparent cytoplasmic vacuolation of hepatocytes around the central vein in wild-type mice fed HF diets for 8 or 16 weeks compared with wild-type mice fed normal diets for 8 or 16 weeks. The degree of hepatic vacuolation increased with the period of feeding. In wild-type mice fed HF diets for 16 weeks, a markedly high level of cytoplasmic vacuolation of hepatocytes around the portal vein was Megestrol Acetate observed compared with that in cells around the central vein. The vacuolated area was not stained with periodic acid-Schiff, which stains glycogen. In contrast to wild-type mice fed HF diets, we found that cytoplasmic vacuolation of hepatocytes around the central and portal veins was strikingly suppressed in IVA-PLA2-knockout mice fed HF diets for 8 weeks. Even after 16 weeks of HF feeding, IVA-PLA2knockout mice exhibited considerably reduced hepatic vacuolation. Under normal dietary conditions, slight cytoplasmic vacuolation was observed in hepatocytes of wild-type mice; however, this was not the case for IVA-PLA2-knockout mice. This observation in mice fed normal diets was consistent with the results shown in our recent paper.