Early steps of Eicosanoid precursor absorption and tissue distribution

Abstract: Eicosanoids are important for a wide range of physiological and pathophysiological processes.How their essential fatty acid precursors are absorbed and tissue distributed is not well charactherized. When given orally to rats, arachidonic acid (20:4) was retained in the small intestine to a larger extent than linoleic acid (18:2).More 20:4 than 18:2 was incorporated in phospholipids (PL) of the small intestine, with the strongest preference for phosphatidyl ethanolamine and phosphatidyl inositol. More of the 20:4 than of 18:2 was directed to the liver. Essential fatty acid deficient (EFAD) rats had an increased incorporation of 18:2 in all tissues, and an increased PL incorporation of both 20:4 and 18:2 compared to controls. EFAD human HepG2 cells had an increased delta-6- and delta-5-desaturase activity. Both enzymes had a rate limiting function.Chylomicron 20:4- and 20:5-diacylglycerol esters were resistant to in vitro incubations with lipoprotein lipase (LPL) but not to hepatic lipase.18:2 and other shorterchain fatty acid esters were not LPL resistant. When 20:4 was injected intravenously to rats, 8% of the dose was secreted in the bile during 24h. Diverting the bile with a drain decreased the recovery of small intestinal 20:4 by 75%, but did not decrease the recovery in stomach and colon. The pools of 20:4 injected i.v. in albumin bound form and injected esterified in chylomicrons did not equilibrate even after 96 h. The selective chanelling of 20:4 to the liver via chylomicrons, and biliary secretion, points to an enterohepatic circulation of 20:4.