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.