Apoprotein A-I Synthesis in Normal Intestinal Mucosa and in Tangier Disease

Abstract

To determine whether human small intestine synthesizes apoA-I, the major apoprotein of plasma high-density lipoproteins, we used immunofluorescence technics and monospecific antiserums to visualize apoA-I within intestinal epithelial cells from four normal subjects and one patient with Tangier disease. Biopsies from all subjects during fasting showed limited fluorescence. After lipid feeding intracellular apoA-I markedly increased in both normal subjects and the patient. During alimentary lipemia, mean plasma apoA-I levels (milligrams per deciliter) increased in four normal subjects from 161 +/- 12 (+/- S.E.M.) to 180 +/- 15 (P less than 0.05) and in the patient from 1.9 to 6.8. Normal plasma chylomicrons contained apoB, apoE and the C peptides but not apoA-I. The patient's chylomicrons contained ap0A-I. Normal and Tangier-disease intestinal-mucosa cells increase their content of apoA-I during chylomicron formation and subsequently contribute to plasma apoA-I levels. The low levels of apoA-I in Tangier disease are not due to a failure of intestinal synthesis but might be due to abnormal metabolism of chylomicron apoproteins.

Effects of Insulin Resistance and Obesity on Lipoproteins and Sensitivity to Egg Feeding

“…31 Like the LDL-C response, the increase in HDL-C in IS subjects with egg feeding is also consistent with an intestinal etiology. Intestinal apo A-I formation is increased with cholesterol and fat feeding, 34,35 and plasma apo A-I levels increase with egg feeding. 12 The slightly greater and more statistically robust percentage increase in HDL-C relative to LDL-C is also in keeping with an intestinal regulation of the HDL-C rise with egg feeding.…”

Small Intestine but Not Liver Lysophosphatidylcholine Acyltransferase 3 (Lpcat3) Deficiency Has a Dominant Effect on Plasma Lipid Metabolism

“…It has been demonstrated that the small intestine is one of the sources of apoA-I in blood (33,34). Plasma apoA-I levels in healthy humans increases after ingestion of a fatty meal (35). Moreover, apoA-I can be transferred from chylomicrons to HDL (36).…”

Human Apolipoprotein A-IV

“…These studies suggest that HDL may be involved in the subsequent metabolism of human apoA-IV even though it is not a major HDL apoprotein in normal plasma. It is of interest that apoA-IV levels determined in one patient with Tangier disease (10,38) were normal (13.6 m0gdl) despite severely reduced HDL and apoA-I levels (10) indicating that apoA-IV does not participate in the abnormal catabolism of chylomicron-HDL apoproteins characteristic of Tangier disease (39,40). In addition, we have observed that some subjects with acquired lecithin cholesterol acyltransferase deficiency resulting from alcoholic hepatitis have apoA-IV as an HDL apoprotein (unpublished results) again suggesting that HDL may be involved in apoA-IV metabolism.…”

“…Intestinal epithelial cells were then isolated from the biopsies and indirect immunofluorescence studies performed using antiserum to apoA-IV as previously described (10,23). Nonimmune rabbit serum and antiserum that had been absorbed with purified apoA-IV served as controls.…”

“…These studies have revealed that human intestinal epitheliumn contains apolipoprotein B (apoB)l (8,9), apoA-I, and apoA-II (10,11) and in vitro isotopic incorporation studies have demonstrated synthesis of these apoproteins (11). Quantitation of apoA-I and apoA-II output in the chylous urine of two subjects with chvluria revealed that the intestine is a major source of these apoproteins for plasma (12).…”