Caco‐2 cells as a model for intestinal lipoprotein synthesis and secretion

Abstract

Caco-2 cells, an intestinal cell line derived from a human colorectal carcinoma that spontaneously differentiates under standard culture conditions, lends itself to the in vitro study of human gut in view of its efficient intestinal transport processes. Among its multiple biological functions are those related to the absorption, transport, and metabolism of lipids and lipoproteins. Despite their intestinal origin, confluent Caco-2 cell monolayers primarily express L-FABP for the uptake of apical dietary long chain fatty acids, incorporating them into triglycerides by the glycerol 3-phosphate pathway, and assembling very-low-density lipoprotein, high-density lipoprotein, and low-density lipoprotein. The monoacyl-glycerol pathway is inactive in Caco-2 cells. Furthermore, the secretion of newly synthesized triglyceride-rich lipoproteins is very restricted, despite abundant production of apolipoprotein (apo) B. The regulation of apoB synthesis and its mRNA editing at the enterocyte level has been intensively examined in Caco-2 cells. Luminal fatty acids, calcium ion, as well as vitamins and hormones are known to modulate the apoB-48/apoB-100 at the transcriptional and/or translational level. The regulation of 3-hydroxy-3-methylglutaryl-CoA reductase and acyl-CoA: (cholesterol acyltransferase), the key enzymes governing intracellular cholesterol handling, have also been extensively examined in Caco-2 cells. In many respects this cell line provides an excellent in vitro model for the investigation of intestinal lipoprotein metabolism; however, their limited secretion capacity remains a potential drawback to comparisons with the in vivo physiological state.

Apolipoprotein B, a Paradigm for Proteins Regulated by Intracellular Degradation, Does Not Undergo Intracellular Degradation in CaCo2 Cells

“…Whether apoB-48 is degraded by proteasome-mediated events in intestinal cells is unknown. We initiated this study to examine the biogenesis of apoB-100 and apoB-48 in a model human intestinal cell line, CaCo2, that has been used extensively to study apoB biogenesis in the past (25). To our surprise, we found that newly synthesized apoB-100 and apoB-48 are quantitatively recovered in the cellular lysate and the medium in CaCo2 cells and do not seem to be subject to proteasome-mediated degradation.…”

Effects of Epidermal Growth Factor and Linoleic Acid on Lipid Contents in Human Intestinal C2BBe1 Cells

“…Additionally, the incubation with EGF at a concentration of 1 nM (6 ng/mL) at least for 4 days significantly increased intracellular triglyceride content in mouse differentiated adipocytes (3T3-L1 cells) by stimulating acyl-CoA synthetase activity, which is the rate-limiting enzyme for adipogenesis (20). Because confluent Caco-2 monolayers primarily express intestinal fatty acid-binding protein for the uptake of long chain fatty acids (14), exogenous linoleic acid can serve as a substrate for lipid synthesis. Similarly, van Greevenbroek et al demonstrated that the addition of 14 C-linoleic acid was efficiently incorporated into triglycerides by Caco-2 cells (17).…”

“…The C2BBe1 cell line, cloned from human colon adenocarcinoma Caco-2 cells, has high homology in morphology compared with Caco-2 cells that was often used as an experimental model for the synthesis, absorption, or transport of macronutrients, minerals, vitamins, or drugs in the intestine (14,15). It is unclear whether linoleic acid also serves a regulatory function in the action of EGF on lipogenesis in the intestinal cells.…”

Avancées dans la dissection fonctionnelle du transport intestinal des lipides

“…Nos observations suggèrent une fonction différente pour les deux : la L-FABP serait probablement chargée de faire converger les AGCL vers le réticulum endoplasmique (RE) pour la formation et la sécrétion des chylomicrons (CM) puisque peu de ces particules sont libérées par les cellules Caco-2 connues pour leur déficience en L-FABP [25,26]. De son côté, la I-FABP ne semble pas prêter son concours à cette voie et semblerait guider les AGCL vers d'autres compartiments intracellulaires.…”