Dietary saturated fatty acids reduce hepatic lipid accumulation but induce fibrotic change in alcohol-fed rats

Background: In this study, we evaluated the influence of an ethanol-containing diet with high saturatedfatty acids (SFAs) on alcoholic liver disease (ALD) in rats.Methods: Male Wistar rats weighing about 160 g were divided into four groups: an ethanol (E) group fedan ethanol-containing liquid diet with 36% total calories as fat (corn oil, olive oil and safflower oil); a control(C) group pair-fed an isoenergetic diet without ethanol; an ethanol with saturated fat (EHS) group fed anethanol-containing diet which contained 40% total calories as fat (90% lard); and a control with saturated fat(CHS) group fed an isoenergetic diet without ethanol, which contained 40% total calories as fat.Results: After 8 weeks of treatment, the liver weight and plasma aspartate aminotransferase (AST)activities in E and EHS groups were significantly higher than those of C group. Significantly higher scoresof inflammation, necrosis, and fatty changes were found in E group, whereas significantly higher scores ofnecrosis, bile duct hyperplasia, and fibrosis were found in EHS group. Although significantly lower plasmaadiponectin concentrations were observed in both E and EHS groups, compared to C group, plasmaadiponectin in EHS group was significantly higher than that in E group. There was no change in hepaticperoxisome proliferator activated receptor (PPAR)-α expression between E and C groups, and rats in EHSgroup showed a significantly elevated level compared to the other groups. A lower hepatic sirtuins (SIRT)-1 level was found in E group, but it did not reach statistical significance. Moreover, the highest plasmaTGF-β1 level was found in EHS group. Compared to C group, the hepatic reduced glutathione/oxidizedglutathione ratio and thiobarbituric acid (TBA)-reactive substance level were significantly increased in Eand EHS groups; however, there was no significant difference between E and EHS groups. Significantlyincreased hepatic CYP2E1 expression was observed in both E and EHS groups, while at the same time,hepatic CYP2E1 in EHS group was the highest among all groups. The hepatic tumor necrosis factor (TNF)-α,interleukin (IL)-1β, IL-6, and IL-10 concentrations in the E group were significantly higher than those in Cgroup, whereas the hepatic IL-6 and IL-10 concentrations in ES group were significantly lower than those ofE group.Conclusions: These results suggested that dietary saturated fats may inhibit hepatic fat accumulation andinduce hepatic fibrosis in rats under chronic alcohol intake.