Although HF diets also increased adipocyte size in IVA-PLA2knockout mice, the adipocytes under the HF dietary conditions were smaller in IVA-PLA2-knockout mice than in wild-type mice. Similar results were observed after 16 weeks of HF feeding. The elevation of serum aminotransferase level, as a marker of liver damage, is correlated with NAFLD. In agreement with this, we show here that the serum level of alanine aminotransferase was significantly higher in wild-type mice fed HF diets for 8 weeks than in wild-type mice fed normal diets, and the serum levels of both ALT and aspartate aminotransferase were markedly increased after 16 weeks of HF feeding. However, no elevation of these aminotransferase levels was observed in IVA-PLA2-knockout mice even under HF dietary conditions. Considering the correlation of hepatic fat deposition with liver damage, it is likely that the protection against the HF diet-induced elevation of serum aminotransferase levels in IVAPLA2-knockout mice is due to the reduced hepatic vacuolation and TG content. It is conceivable that changes in the levels of adipokines including adiponectin, leptin, and resistin influence the accumulation of intracellular lipids in the liver. Taking this into account, we determined the serum levels of adipokines in wild-type and IVA-PLA2-knockout mice fed normal or HF diets. As shown in Figure 6A, HF diets taken for 8 weeks did not affect the serum levels of adiponectin in wild-type and IVA-PLA2-knockout mice. In contrast, HF diets increased the serum levels of leptin in both genotypes, with no difference Pranoprofen exhibited between the levels in the two groups. Furthermore, no significant difference was observed in the serum levels of resistin among the four groups under our experimental conditions. Fatty liver with hepatocellular damage occurs in parallel with the accumulation of hepatic TG, which is associated with abdominal obesity. The present study showed that HF feeding of wild-type mice increased hepatocellular vacuolation, hepatic TG Sulpiride content, and serum aminotransferase levels with increases in adipose tissue mass and the number of hypertrophic adipocytes, indicating that HF diet-fed wild-type mice exhibited fatty liver damage with adipose fat deposition.