Increased plasma oleoylethanolamide and palmitoleoylethanolamide levels correlate with inflammatory changes in alcohol binge drinkers: the case of HMGB1 in women

Alcohol binge drinking is a heavy pattern of alcohol consumption increasingly used by young people. In a previous study, we reported that young drinkers with a 2-year history of binge alcohol consumption had an overactivation of the innate immune system and peripheral inflammation when compared with controls. In the present study, we measured several biolipids that are fatty acid derivatives belonging to the acylethanolamide or 2-acylglycerol families in the plasma of the same subjects (n = 42; 20 men and 22 women). We found that during abstinence, alcohol binge drinkers had elevated plasma levels of oleoylethanolamide, palmitoleoylethanolamide, arachidonoylethanolamide, dihomo-gamma-linolenoyl ethanolamide and linoleoyl ethanolamide, which positively correlated with changes in the mRNA expression of key inflammatory markers in peripheral blood mononuclear cells, such as toll-like receptors (TLR4), pro-inflammatory cytokines/chemokines interleukin-1 beta, interleukin-6 and monocyte chemoattractant protein-1, and cyclooxygenase-2. Additionally, plasma oleoylethanolamide positively correlated with plasma levels of high mobility group box-1, which is a danger-associated molecular pattern and an endogenous TLR4 agonist, specifically in female alcohol binge drinkers. No changes were observed in 2-acylglycerols in alcohol binge drinkers, although sex-related differences in these bioactive lipids as well as in palmitoleoylethanolamide and docosatetraenoylethanolamide levels were detected. These results extend the previous clinical findings observed in patients diagnosed with long-term alcohol use disorder to young users and suggest a prominent role for these lipids in the response to acute alcohol exposure.