Differentiated CaCo-2 cells as an in-vitro model to evaluate de-novo apolipoprotein A-I production in the small intestine

Eur J Gastroenterol Hepatol. 2009 Jun;21(6):642-9. doi: 10.1097/meg.0b013e328321b0c8.

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).

Conclusion: 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.

Publication types

  • Evaluation Study

MeSH terms

  • Anticholesteremic Agents / pharmacology
  • Apolipoprotein A-I / biosynthesis*
  • Butyrates / pharmacology
  • Caco-2 Cells
  • Cell Differentiation
  • Drug Evaluation, Preclinical
  • Hep G2 Cells
  • Humans
  • Intestine, Small / drug effects
  • Intestine, Small / metabolism*
  • Isoxazoles / pharmacology
  • Models, Biological*
  • Peroxisome Proliferators / pharmacology
  • Phenylurea Compounds / pharmacology
  • Pyrimidines / pharmacology
  • Receptors, Cytoplasmic and Nuclear / agonists

Substances

  • Anticholesteremic Agents
  • Apolipoprotein A-I
  • Butyrates
  • GW 7647
  • Isoxazoles
  • Peroxisome Proliferators
  • Phenylurea Compounds
  • Pyrimidines
  • Receptors, Cytoplasmic and Nuclear
  • farnesoid X-activated receptor
  • pirinixic acid
  • GW 4064