APOA5 gene expression in the human intestinal tissue and its response to in vitro exposure to fatty acid and fibrate.

BACKGROUND AND AIMS

APOA5, a key gene regulating triglyceride (TG) levels, is reported to be expressed exclusively in the liver where it may regulate TG-rich particle synthesis and secretion. Since the same lipoprotein processing occurs in the intestine, we have postulated that this organ would also express APOA5.

METHODS AND RESULTS

We have detected the APOA5 gene expression in C57BL/6J mouse and in human small intestine samples. In humans, it is expressed mainly in the duodenum and colon, with messenger RNA (mRNA) levels four orders of magnitude lower than in the liver, and the protein product being one-sixth of the liver equivalent. Subsequently, we carried out in vitro experiments in TC-7/CaCo(2) human intestinal cells to analyse the expression of APOA5, APOC3, APOB and MTP genes after the incubation with long- and short-chain fatty acids, and a peroxisome proliferator-activated receptor alpha (PPARα) agonist (Wy 14643, a fibrate therapeutic agent). In the TC-7 cell line, APOA5 expression was significantly upregulated by saturated fatty acids. The short-chain fatty acid butyrate increased APOA5 expression almost fourfold while APOB was downregulated by increasing butyrate concentrations. When TC-7 cells were incubated with PPARα agonist, the APOA5 expression was increased by 60%, while the expression of APOB, MTP and APOC3 was decreased by 50%, 30% and 45%, respectively.

CONCLUSION

Our results demonstrate that APOA5 is expressed in the intestine, albeit at a much lower concentration than in the liver. While it remains to be determined whether intestinal apo A-V is functional, our in vitro experiments show that its expression is modifiable by dietary and pharmacological stimuli.