Adiponectin levels were comparable, showing no differences among

the groups; however, LFD+VDD, WD and WD+VDD animals had higher leptin than LFD animals (Table 3). There were no significant differences in plasma IL-1β serum levels (LFD 14.0 ± 6.6 pg/mL, LFD+VDD 21.6 ± 11.1, WD 34.7 ± 26.2, WD+VDD 61.9 ± 47 pg/mL). IL-6 plasma levels were below the detection www.selleckchem.com/products/LBH-589.html level of the assay (<5 pg/mL) in LFD groups but were detectable in WD (143 ± 138 pg/mL) and WD+VDD (90 ± 54 pg/mL) (t test, NS). Serum LBP levels were significantly higher in WD than in LFD groups (LFD: 878 ± 31, LFD+VDD 936 ± 21, WD: 1,373 ± 209, WD+VDD 1,493 ± 242 ng/mL, P < 0.05 WD versus LFD groups). Hepatic steatosis and lobular inflammation were lower in LFD animals and this was unaffected by VDD. There was no significant difference in hepatic steatosis and lobular inflammation between LFD and WD animals, in part due to variability in responses. In WD+VDD animals, we found increased hepatic steatosis and lobular inflammation. Lobular inflammation and NAS were significantly higher in WD+VDD relative to all other groups. Moreover, there was a trend for higher ballooning score in WD+VDD rats compared to the other groups (Table 4, Fig. 1A-D). After the 10 weeks of dietary exposures, there was no significant fibrosis that fulfilled the NASH CRN criteria in zones 1 or 3 (Fig. 1E); however, incipient check details perivenular/pericellular

fibrosis was seen in 3 WD+VDD rats (Fig. 1F). Gene expression studies were executed to determine whether increased NASH was accompanied by increased inflammation. VDD had a greater effect on inflammatory genes in the liver compared to adipose tissue. Specifically, liver resistin mRNA levels were higher in VDD groups compared to VitD replete animals (Fig. 2A), but no differences between groups were seen in adipose tissue (data not shown). IL-4 mRNA levels were higher

in VDD than in VitD replete groups, with greater effect exhibited in liver than adipose tissue (Fig. 2B; Supporting Fig. 2A). IL-6 mRNA levels were higher in VDD than in VitD replete groups in the liver (Fig. 2C), and higher in WD+VDD compared to all other groups Dolichyl-phosphate-mannose-protein mannosyltransferase in adipose tissue (Supporting Fig. 2B). Further examination of hepatic signaling pathways involved in inflammation and oxidative stress in liver revealed activation of IL-1β in both WD and VDD independently (Fig. 2D), and activation of IL-10 by WD (Fig. 2E), whereas in adipose tissue IL-1β did not differ significantly between the groups (data not shown). Liver mRNA levels for HO-1, a marker for oxidative stress, were significantly higher in WD+VDD versus WD rats (Fig. 2F). Analysis of the TLR signaling pathways showed activation of TLR4 and LBP in both WD and VDD independently (Fig. 3A,B), activation of CD14, TLR2, TIRAP, and TLR9 by WD with further increment by VDD (Fig.