Based on these findings, Laposata and Lange (130) proposed that FAEEs, independent of acetaldehyde, contribute to or exacerbate alcohol-induced organ damage. Data from several pre-clinical studies support this hypothesis. First, arterial administration of FAAEs in rats induces a phenotype characteristic of acute pancreatitis (131). Second, promoting FAEE synthesis (by inhibiting the oxidative pathway) worsens symptoms of alcohol-associated acute pancreatitis (132) while inhibiting FAEE synthesis (through pharmacological inhibition of an FAEE synthase) alleviates these symptoms in experimental models, both in vitro and in vivo (133).
