title: Differentiated CaCo-2 cells as an in-vitro model to evaluate  de-novo apolipoprotein A-I production in the small intestine.
abstract: BACKGROUND
  Increasing HDL cholesterol concentrations by stimulating de-novo apolipoprotein A-I (apoA-I) production in the liver and/or in the small intestine is a potential strategy to reduce coronary heart disease risk. Although there is quite some knowledge concerning regulatory effects in the liver, less is known concerning potential agents that could elevate de-novo apoA-I production in the small intestine.
  
  
  METHODS
  Therefore, we compared side-by-side effects of various peroxisome proliferator-activated receptor (PPAR)alpha, PPARgamma, retinoid-X-receptor alpha, and farnesoid-X-receptor agonists on de-novo apoA-I production in differentiated CaCo-2 and HepG2 cells.
  
  
  RESULTS
  For PPARa agonists, we showed that GW7647 elevated apoA-I concentrations in the medium of both cell models, whereas WY14643 elevated only de-novo apoA-I concentrations in differentiated CaCo-2 cells. Unexpectedly, fenofibric acid lowered apoA-I medium concentrations in both cell lines, which could not be explained by a lack of PPAR transactivation or a lack of retinoid-X-receptor a activation. For farnesoid-X-receptor agonists, chenodeoxycholic acid strongly reduced apoA-I concentrations both in differentiated CaCo-2 and HepG2 cells, whereas GW4064 and taurocholate only lowered apoA-I in CaCo-2 cells (GW4064) or in HepG2 cells (taurocholate). However, overall effects of all individual components on apoA-I production in differentiated CaCo-2 and HepG2 cells were highly correlated (r = 0.68; P = 0.037; N=9).
  
  
  CONCLUSIONS
  We conclude that differentiated CaCo-2 cells are suitable models to study de-novo small intestinal apoA-I production in vitro enabling the possibility to screen for potential bioactive dietary components. This cell model may also determine small-intestinal-specific effects, as some discrepancy was found between both cell models.
authors.affiliation: Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
authors.forename: Stefan P J
authors.initials: SP
authors.lastname: Dullens
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Mensink
authors.forename: Edwin C M
authors.initials: EC
authors.lastname: Mariman
authors.forename: Jogchum
authors.initials: J
authors.lastname: Plat
mesh_terms: D000924:Anticholesteremic Agents / Q000494:pharmacology; D016632:Apolipoprotein A-I / Q000096:biosynthesis*; D002087:Butyrates / Q000494:pharmacology; D018938:Caco-2 Cells; D002454:Cell Differentiation; D004353:Drug Evaluation, Preclinical; D056945:Hep G2 Cells; D006801:Humans; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism*; D007555:Isoxazoles / Q000494:pharmacology; D008954:Models, Biological; D020025:Peroxisome Proliferators / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D000924:Anticholesteremic Agents; D016632:Apolipoprotein A-I; D002087:Butyrates; D007555:Isoxazoles; D020025:Peroxisome Proliferators; D010671:Phenylurea Compounds; D011743:Pyrimidines; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated; C453899:GW 7647; C006253:pirinixic acid; C412815:GW 4064