Adaptation of enterocytic Caco-2 cells to glucose modulates triacylglycerol-rich lipoprotein secretion through triacylglycerol targeting into the endoplasmic reticulum lumen.
Enterocytes are responsible for the absorption of dietary lipids, which involves TRL [TG (triacylglycerol)-rich lipoprotein] assembly and secretion. In the present study, we analysed the effect on TRL secretion of Caco-2 enterocyte adaptation to a differential glucose supply. We showed that TG secretion in cells adapted to a low glucose supply for 2 weeks after confluence was double that of control cells maintained in high-glucose-containing medium, whereas the level of TG synthesis remained similar in both conditions. This increased secretion resulted mainly from an enlargement of the mean size of the secreted TRL. The increased TG availability for TRL assembly and secretion was not due to an increase in the MTP (microsomal TG transfer protein) activity that is required for lipid droplet biogenesis in the ER (endoplasmic reticulum) lumen, or to the channelling of absorbed fatty acids towards the monoacylglycerol pathway for TG synthesis. Interestingly, by electron microscopy and subcellular fractionation studies, we observed, in the low glucose condition, an increase in the TG content available for lipoprotein assembly in the ER lumen, with the cytosolic/microsomal TG levels being verapamil-sensitive. Overall, we demonstrate that Caco-2 enterocytes modulate TRL secretion through TG partitioning between the cytosol and the ER lumen according to the glucose supply. Our model will help in identifying the proteins involved in the control of the balance between TRL assembly and cytosolic lipid storage. This mechanism may be a way for enterocytes to regulate TRL secretion after a meal, and thus impact on our understanding of post-prandial hypertriglyceridaemia.
Pauquai
Thomas
T
UMR 505 INSERM-Université Pierre et Marie Curie and Laboratoire de Pharmacologie Cellulaire de l'Ecole Pratique des Hautes Etudes, Centre de Recherches Biomédicales des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France.
Bouchoux
Julien
J
Chateau
Danielle
D
Vidal
Romain
R
Rousset
Monique
M
Chambaz
Jean
J
Demignot
Sylvie
S
D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism; D000222:Adaptation, Physiological; D001055:Apolipoproteins B / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D018938:Caco-2 Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D020895:Enterocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D005947:Glucose / Q000494:pharmacology*; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D008074:Lipoproteins / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology
D001055:Apolipoproteins B; D002352:Carrier Proteins; D008074:Lipoproteins; D012333:RNA, Messenger; D014280:Triglycerides; C106092:microsomal triglyceride transfer protein; D006003:Glycogen; D014700:Verapamil; D000217:Acyltransferases; C021802:2-acylglycerol O-acyltransferase; D005947:Glucose