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

The effect of heritability and host genetics on the gut microbiota and metabolic syndrome

“…This finding suggests that the APOA5 variant may contribute to the compositional change of the MetS-related gut microbiota. The APOA5 gene is predominantly expressed in the liver, but is also produced at a low level in the intestine 22. The regulatory role of APOA5 in triglyceride metabolism has been demonstrated extensively in mice and humans, especially in liver and plasma 18 50.…”

“…The rs651821 SNP, located 3 bp upstream from the start codon of APOA5 , showed significant associations with increased risk of hypertriglyceridaemia or MetS in various populations 19–21. Because APOA5 is also expressed in the intestine, although at a considerably lower level than in the liver,22 we hypothesised that there would be a relationship between the APOA5 SNP rs651821 and the gut microbiota, and that such relationship might be associated with MetS.…”

Tissue-specific DNA methylation profiles regulate liver-specific expression of the APOA1/C3/A4/A5 cluster and can be manipulated with demethylating agents on intestinal cells

“…Although it is reported that the APOA1/C3/A4/A5 genes are expressed almost exclusively in the liver, work by our group [31] and others have shown that these transcripts are also expressed at low levels in the small intestine [33]. In the present study we hypothesize that intestinal APOA1/C3/A4/A5 gene cluster expression is regulated by epigenetic mechanisms, including DNA methylation, and that altering these mechanisms would result in enhanced expression.…”

“…We previously described that APOA5 is expressed at low levels in intestinal samples from mice and humans [31] and that compared with its expression in the liver, intestinal APOA5 expression levels were approximately 32,000 and 1000-fold lower in humans and mice, respectively, while its protein levels were 6-fold lower in an intestinal cell line compared to that in hepatic cells. So, even if we have been able to increase intestinal APOA5 levels, we have not been able to reach the expression levels in the liver.…”

“…Revision A. Foster city [CA]: Applied Biosystems, 1997) using GAPDH gene expression as endogenous control because in previous studies it showed high consistency [31].…”