n-3 Polyunsaturated fatty acids for the management of alcoholic liver disease: A critical review

Excess alcohol exposure leads to alcoholic liver disease (ALD), a predominant cause of liver-related morbidity and mortality worldwide. In the past decade, increasing attention has been paid to understand the association between n-3 polyunsaturated fatty acids (n-3 PUFAs) and ALD. In this review, we summarize the metabolism of n-3 PUFAs, animal model of ALD, and the findings from recent studies determining the role of n-3 PUFAs in ALD as a possible treatment. The animal models of acute ethanol exposure, chronic ethanol exposure and chronic-plus-single binge ethanol feeding have been widely used to explore the impact of n-3 PUFAs. Although the results of studies regarding the role of n-3 PUFAs in ALD have been inconsistent or controversial, increasing evidence has demonstrated that n-3 PUFAs may be useful in alleviating alcoholic steatosis and alcohol-induced liver injury through multiple mechanisms, including decreased de novo lipogenesis and lipid mobilization from adipose tissue, enhanced mitochondrial fatty acid beta-oxidation, reduced hepatic inflammation and oxidative stress, and promoted intestinal homeostasis, positively suggesting that n-3 PUFAs might be promising for the management of ALD. The oxidation of n-3 PUFAs ex vivo in an experimental diet was rarely considered in most n-3 PUFA-related studies, likely contributing to the inconsistent results. Thus, the role of n-3 PUFAs in ALD deserves greater research efforts and remains to be evaluated in randomized, placebo-controlled clinic trial.