Human apolipoprotein A-IV. Intestinal origin and distribution in plasma.
The role of the human intestine has been explored as a site of synthesis of apoA-IV, a major apoprotein of human intestinal triglyceride-rich lipoproteins. Intestinal biopsies were performed on normal volunteers while fasting and after lipid ingestion. Indirect immunofluorescence demonstrated a marked increase in immunofluorescence for apoA-IV during lipid absorption consistent with an increased intracellular content. ApoA-IV comprised 10-13% of chylomicron apoprotein and 24-30% of intestinal very low density lipoprotein (VLDL) as assessed by densitometry of sodium dodecyl sulfate gels of lipoproteins from chylous urine (mesenteric lymphatic-urinary fistula) and thoracic duct lymph (postoperative fistula). After one subject with chyluria ingested 40 g of corn oil, triglyceride excretion in urine was accompanied by an increased excretion of apoA-IV. 11.5 g of triglyceride and 81 mg of apoA-IV were recovered in the urine. In chylous urine 56% of apoA-IV was in the triglyceride-rich lipoproteins (chylomicrons and intestinal VLDL) and 44% in the d > 1.006-g/ml fraction. Normal plasma apoA-IV was 15.7+/-0.9 mg/dl (n = 14) whereas four subjects with abetalipoproteinemia had reduced levels 1.2, 7.6, 9.6, and 8.3 mg/dl, respectively. Lipid feeding in normal volunteers resulted in a rise in plasma apoA-IV (16.1+/-0.7 mg/dl to 18.5+/-0.7 mg/dl, n = 5, P < 0.01). In fasting plasma, 98% of apoA-IV was in the d > 1.21-g/ml fraction. In lipemic plasma, 10% of apoA-IV was associated with triglyceride-rich lipoproteins and 90% with the d > 1.21-g/ml fraction. Agarose column chromatography of fasting plasma confirmed that the bulk of plasma apoA-IV is free, unassociated with lipoproteins. These results demonstrate that apoA-IV is present in human intestinal epithelial cells and is secreted as a chylomicron and VLDL apoprotein. Within fasting plasma most of the apoA-IV is found free, unassociated with lipoproteins. After lipid ingestion apoA-IV is also found in plasma chylomicrons indicating that some apoA-IV remains associated with chylomicrons in plasma during chylomicron metabolism, although some may be transferred from the chylomicron surface.
D001053:Apolipoproteins / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D001054:Apolipoproteins A; D002913:Chyle / Q000378:metabolism; D004041:Dietary Fats; D004591:Electrophoresis, Polyacrylamide Gel; D005455:Fluorescent Antibody Technique; D006801:Humans; D007122:Immunoelectrophoresis; D007413:Intestinal Mucosa / Q000378:metabolism*; D008055:Lipids / Q000097:blood; D008297:Male; D014556:Urine
D001053:Apolipoproteins; D001054:Apolipoproteins A; D004041:Dietary Fats; D008055:Lipids; C022205:apolipoprotein A-IV