Abstract
The role of n-3 polyunsaturated fatty acids (PUFAs) in alcoholic liver disease (ALD) has been controversial. N-3 PUFA oxidation in animal feeding stuffs was rarely concerned, likely contributing to inconsistent outcomes. Here, we report the impacts of oxidized fish oil (OFO) on ALD in C57BL/6 mice. Alcohol exposure increased plasma aminotransferase levels and hepatic inflammation. These deleterious effects were ameliorated by unoxidized FO but exacerbated by OFO. Sequencing analysis showed the accentuated intestinal dysbiosis and the increased proportion of Proteobacteria in OFO-fed mice. Intestinal sterilization by antibiotics completely abolished OFO-aggravated liver injury. Additionally, alcohol exposure leads to the greater increase in plasma endotoxin and decrease in intestinal tight junction protein expressions in OFO-fed mice. Stabilization of intestinal barrier by obeticholic acid markedly blunted OFO-aggravated liver injury in alcohol-fed mice. These results demonstrate that OFO exacerbates alcoholic liver injury through enhancing intestinal dysbiosis, barrier dysfunction, and hepatic inflammation mediated by gut-derived endotoxin.
Highlights
The role of n-3 polyunsaturated fatty acids (PUFAs) in alcoholic liver disease (ALD) has been controversial
After air exposure at 65 °C for 2 weeks, oxidized fish oil (OFO) showed the higher degree of oxidation as evidence by the greatly elevated levels of peroxide value (POV), p-anisidine value (AV), total oxidation value (Totox), and thiobarbituric acid-reactive substances (TBARS), compared to the unoxidized fish oil (FO) (Table 1)
These results indicate that hepatic steatosis and oxidative stress induced by alcohol exposure are exacerbated by dietary OFO but reversed by FO
Summary
The role of n-3 polyunsaturated fatty acids (PUFAs) in alcoholic liver disease (ALD) has been controversial. Alcohol exposure increased plasma aminotransferase levels and hepatic inflammation These deleterious effects were ameliorated by unoxidized FO but exacerbated by OFO. Alcohol exposure leads to the greater increase in plasma endotoxin and decrease in intestinal tight junction protein expressions in OFO-fed mice. Stabilization of intestinal barrier by obeticholic acid markedly blunted OFO-aggravated liver injury in alcohol-fed mice. These results demonstrate that OFO exacerbates alcoholic liver injury through enhancing intestinal dysbiosis, barrier dysfunction, and hepatic inflammation mediated by gut-derived endotoxin. Alcohol exposure impairs intestinal barrier integrity, leading to the increased intestinal permeability, and subsequent the enhanced translocation of bacteria and LPS to the portal circulation[6]. Several studies have shown that the supplement of n-3-rich fish oil (FO)
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