Lipid micelles stimulate the secretion of triglyceride-enriched apolipoprotein B48-containing lipoproteins by Caco-2 cells.
Intestinal triglyceride-rich lipoproteins (TRL) are synthesized from dietary lipids. This study was designed to evaluate the effects of lipid micelles, mimicking post-digestive duodenal micelles, on the fate of apolipoprotein B (apoB)48-containing lipoproteins by Caco-2 cells. Such micelles, consisting of oleic acid (OA), taurocholate, 2-monooleoylglycerol (2-MO), cholesterol (Chol), and L-alpha-lysophospatidylcholine, were the most efficient inducers of OA uptake and esterification. The efficiency of TG and apoB48 secretion increased specifically as a function of cell differentiation. PAGE analysis of secreted lipoproteins separated by sequential ultracentrifugation after [35S] labeling revealed differences in the secretion of apoB100- and apoB48-containing lipoproteins. In absence of micelles, apoB48 was secreted mostly in "HDL-like" particles, as observed in enterocytes in vivo. Micelle application increased 2.7-fold the secretion of apoB, resulting in 53 times more apoB48 being recovered as TG-enriched lipoproteins at d < 1.006 g/ml. Electron microscopy revealed the presence of lipid droplets in the secretory pathway and the accumulation of newly synthesized TG in cytoplasmic lipid droplets, as in enterocytes in vivo. We showed that these droplets could be used for secretion. However, apoB48 preferentially bound to newly synthesized TG in the presence of micelles, accounting in part for the functional advantage of apoB editing in the intestine. While Caco-2 cells express both apoB isoforms, our results show that the apical supply of complex lipid micelles favors the physiological route of apoB48-containing TG-enriched lipoproteins.
Chateau
Danielle
D
UMR505 INSERM-UPMC, Laboratoire de Pharmacologie Cellulaire et Moléculaire de l'EPHE, Paris, France.
Pauquai
Thomas
T
Delers
François
F
Rousset
Monique
M
Chambaz
Jean
J
Demignot
Sylvie
S
D053283:Apolipoprotein B-48; D001055:Apolipoproteins B / Q000378:metabolism*; D018938:Caco-2 Cells; D020895:Enterocytes / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D008074:Lipoproteins / Q000737:chemistry / Q000378:metabolism*; D008823:Micelles; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism*
D053283:Apolipoprotein B-48; D001055:Apolipoproteins B; D008055:Lipids; D008074:Lipoproteins; D008823:Micelles; D014280:Triglycerides