Synthesis and lymphatic transport of intestinal apolipoprotein A-IV in response to graded doses of triglyceride

Factors regulating the intestinal synthesis and secretion of apoA-IV are incompletely understood. Although it is known that apoA-IV is stimulated by dietary lipid, it is not known whether graded doses of triglyceride elicit graded responses in apoA-IV synthesis and secretion. We used the chronic intestinal lymph-fistula rat to examine the effect of graded levels of intestinal triglyceride transport on secretion of apoA-IV into lymph and synthesis of apoA-IV in various regions of intestine. Rats were implanted with chronic duodenal and intestinal lymph duct cannulas and infused with lipid emulsions containing 5, 10, 20, 40, 80 micromoles triolein (including [3H]triolein, 1.2 microcuries), 8.7 micromoles phosphatidylcholine, and 57 micromoles sodium taurocholate in 3 ml phosphate-buffered saline (pH 6.4) at 3 ml/h for 8 h. Lymph samples were collected for 1 h prior to and at 2, 4, 5, 6, 7, and 8 h after the start of lipid infusion. Lymphatic output of triglyceride, phospholipid, and apoA-IV was measured. Steady-state (8 h) content of radioactive lipid was also measured in the lumen and the wall of the gut. In separate studies rats were given infusions of either 5% glucose in saline ("fasting") or triolein emulsion (10, 20, 40, 80 micromoles/h) for 8 h after which incorporation of [3H]leucine into apoA-IV in isolated, in situ loops of duodenum, proximal jejunum, mid-distal jejunum, and terminal ileum was measured. Lipid output increased dose-dependently in response to triolein infusion, with steady-state lipid transport achieved by 5 h after start of lipid infusion. Total recovery of 3H-labeled lipid was similar for all triolein doses. Increase in lymphatic apoA-IV output lagged that of triglyceride by 3-4 h, but by 8 h showed graded increases with triolein dose. ApoA-IV synthesis (apoA-IV radioactivity immunoprecipitated by an apoA-IV monospecific antibody and expressed as % of trichloroacetic acid-precipitable [3H]leucine radioactivity) in the duodenum and proximal jejunum showed a 2-fold increase (compared with fasting) in response to 10 micromoles triolein/h, but no further increase at higher doses. However, apoA-IV synthesis in mid to distal jejunum increased dose-dependently. These results demonstrate 1) graded increases in lymphatic lipid and apoA-IV output, suggesting that lipid-elicited stimulation of apoA-IV output may depend upon the length of intestine recruited for lipid transport; 2) support for the hypothesis that some factor(s) associated with assembly and transport of chylomicrons stimulates output of apoA-IV; 3) apoA-IV synthesis in the proximal jejunum is sensitive to low levels of triglyceride; 4) above that threshold, jejunal apoA-IV synthesis is maximally stimulated, independent of triolein dose; and 5) graded doses of triolein produce increases in intestinal mucosal synthesis of apoA-IV along a proximal-distal gradient.