Glucose and galactose regulate intestinal absorption of cholesterol.

A dose-dependent increase in cholesterol absorption was induced by glucose addition (0-75 mM) to the apical medium of TC7 cells, a well-characterized clone of Caco-2. The uptake into the cells and the secretion rate to the basolateral space were both enhanced by glucose and galactose. This up-regulation was suppressed by SGLT1 inhibition but not by GLUT2 inhibition. Cholesterol cell uptake was significantly decreased by PMA and increased by chelerythrine, with more pronounced changes in the presence of hexoses. Thus, the involvement of a protein kinase C signalling pathway was evidenced in the regulation processes of intestinal cholesterol absorption. In the presence of antibodies directed to hSR-BI cholesterol absorption was reduced by 40% and glucose or galactose no longer enhanced it. We suggest that glucose or galactose, through an interaction with SGLT1, activates a protein kinase C pathway that regulates the activity of one of the intestinal cholesterol transporters, namely hSR-BI.

Functional characterization of three clones of the human intestinal Caco-2 cell line for dietary lipid processing.

We aimed to improve the use of the human intestinal Caco-2 cell line for studying dietary lipid and cholesterol processing by using isolated pure clones (Chantret et al. 1994). Three clones (TC7, PD7 and PF11) were grown as monolayers on semi-permeable filters and compared for cell viability, fatty acid and cholesterol apical uptake or basolateral secretion, apolipoprotein B-48 basolateral secretion and 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase activity. The TC7 clone showed the best viability upon apical incubation with mixed micelles and should be preferred for routine work. Short-term (3.0 h) rates of apical uptake of cholesterol were not different with the three clones, whereas the rate of apical uptake of oleic acid (18:1) was lower (P<0.05) with PF11 (250.6 nmol/mg) and the basolateral secretion of cholesterol and oleic acid was lower with the TC7 clone (0.40 and 29.1 nmol/mg respectively). The secretion of apolipoprotein B-48 basolaterally was about 2-fold lower than from PD7 clone. The basal levels of HMG-CoA reductase activity were significantly different (P<0.05; TC7>PF11 >PD7). The down-regulation of the enzyme activity was moderate (range 13.8-21.0%) and comparable in the presence of apical micellar cholesterol, but was much marked upon basolateral incubation with LDL (range 34.0-53.6%), especially for the PD7 clone. In conclusion, the Caco-2 clones characterized here proved to be particularly suitable for studying lipid nutrients processing. Because these three clones exhibit some different metabolic capabilities, they provide a new tool to study intestinal response to lipid nutrients.