Apolipoprotein A-IV synthesis in proximal jejunum is stimulated by ileal lipid infusion

Biosynthesis of apolipoprotein A-IV (apo A-IV) is stimulated by dietary lipid, but the precise mechanisms involved are not clearly understood. Using an intestinally infused rat model, we compared the effect of delivery of lipid into different intestinal sites on mucosal synthesis of apo A-IV in the jejunum and ileum to determine 1) the effect of lipid delivered to one region of the intestine on apo A-IV synthesis in another region of the gut, and 2) whether any such effect is dependent on the presence of lipid in the latter region. Duodenal infusion of triolein emulsion (40 mumol/h) increased jejunal apo A-IV synthesis and mRNA levels by two- to threefold but had no effect on ileal apo A-IV synthesis or mRNA abundance. Ileal infusion of lipid emulsion containing monoolein (20 mumol/h) + oleic acid (40 mumol/h) stimulated apo A-IV synthesis in both ileum and proximal jejunum. Retrograde (orad) transport of ileally infused lipid was not a likely explanation for the ileal effect on jejunal apo A-IV synthesis, because there was negligible luminal and mucosal recovery of [14C]oleic acid in the jejunum after ileal infusion. Total bile diversion did not block the effect of ileal lipid on jejunal apo A-IV synthesis. Ileal, but not duodenal, lipid infusion stimulated apo A-IV synthesis in a jejunal Thiry-Vella fistula, and perfusion of an ileal Thiry-Vella fistula marginally stimulated proximal jejunal apo A-IV synthesis. Thus administration of lipid to the distal gut produces an increase in mucosal synthesis of apo A-IV in both proximal and distal gut. This effect appears to be independent of direct jejunal presence of lipid, suggesting that lipid in the distal intestine may elicit a signal capable of stimulating jejunal synthesis of apo A-IV.