The Molecular Biological Mechanism of Fish Oil on Preventing Alcoholic Liver Diseases: The Hepatoprotective Effects of EPA and DHA Based on Lipid Metabolism, Autophagy and Inflammatory Responses

To our knowledge, there are few reports which investigate the relationships between the different proportion of fish oil in the liquid diet and alcoholic liver diseases. According the results of previous NSC funding project (NSC 100-2320-B-038 -023 -MY3), it was demonstrated that the partial replacement of olive oil with fish oil could ameliorate the alcoholic fatty liver and hepatitis in rats. This three-year study will follow the previous NSC funding projects in order to demonstrate the biological molecular mechanism of fish oil on the prevention of alcoholic fatty liver and hepatitis in chronic ethanol-fed rats. Male Wistar rats will be divided into six groups according to aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and feed with either control diet or ethanol diet, in which the fat composition of both diets was adjusted with 25% (M:P=1:0.7) or 57% (M:P=1:1.5) fish oil substitution for olive oil. In the first year, we will investigate the effects of fish oil on the biological molecular regulating factors involved in the lipid metabolism in rats fed with ethanol. The analysis will include the liver damage indicators and biological molecular factors related with lipid metabolism, such as SREBP-lc, PPAR-a and their target genes (FSA, SCD1, ACC1, CPT1, ACO, MCAD)。In the second year, we will demonstrate the effects of fish oil on the autophagy in rats fed with ethanol. The measurement will include autolysosome observation, LC3I, LC3II and pAkt/Akt、mTOR 、Beclin-1、p62. In the third year, we will discuss the biological molecular effects of fish oil on the ethanol-induced inflammatory responses in rats by changing the intestinal permeability and microflora. The indicators will include TLR 4 protein (MD-2, CD14), TLR adaptor (MyD88、TRIF、 MAPK、JNK) and transcription factors (NFkB、AP-1).