Dietary saturated fatty acids reverse inflammatory and fibrotic changes inrat liver despite continued ethanol administration

We investigated the potential of dietary saturated fatty acids to reverse a lcoholic liver injury despite continued administration of alcohol. Five gro ups (six rats/group) of male Wistar rats were studied. Rats in groups 1 and 2 were fed a fish oil-ethanol diet for 8 and 6 weeks, respectively. Rats i n groups 3 and 4 were fed fish oil and ethanol for 6 weeks before being swi tched to isocaloric diets containing ethanol with palm oil (group 3) or med ium-chain triglycerides (MCTs, group 4) for 2 weeks. Rats in group 5 were f ed fish oil and dextrose for 8 weeks. Liver samples were analyzed for histo pathology, lipid peroxidation, nuclear factor-kappaB (NF-kappaB) activation , and mRNAs for cyclooxygenase-2 (Cox-2) and tumor necrosis factor-alpha (T NF-alpha). Endotoxin in plasma was determined. The most severe inflammation and fibrosis were detected in groups 1 and 2, as were the highest levels o f endotoxin, lipid peroxidation, activation of NF-kappaB, and mRNAs for Cox -2 and TNF-alpha. After the rats were switched to palm oil or MCT, there wa s marked histological improvement with decreased levels of endotoxin and li pid peroxidation, absence of NF-kappaB activation, and reduced expression o f TNF-alpha and Cox-2. A diet enriched in saturated fatty acids effectively reverses alcohol-induced necrosis, inflammation, and fibrosis despite cont inued alcohol consumption. The therapeutic effects of saturated fatty acids may be explained, at least in part, by reduced endotoxemia and lipid perox idation, which in turn result in decreased activation of NF-kappaB and redu ced levels of TNF-alpha and Cox-2.