HDL LEVELS DO NOT IMPACT ON THE EXPRESSION OF GENES PLAYING A PIVOTAL ROLE IN INTESTINAL LIPID METABOLISM IN APOLIPOPROTEIN E-KNOCKOUT MICE

Background and Aims: We investigated the impact of genetic manipulation of apoA-I/HDL levels on plasma lipids, atherosclerosis development and expression of genes with a pivotal role in lipid metabolism in the three segments of the small intestine. Methods: Mice with extremely low plasma HDL levels, deficient for both murine apoA-I and apoE (DKO), were compared with mice characterized by elevated HDL, deficient for both apoA-I/apoE, but overexpressing human apoA-I (DKO/hA-I). Eight-week-old mice (n¼8-16) were fed chow diet for 16 weeks. Plasma lipids were evaluated and atherosclerosis development at the aortic sinus quantified. Intestinal gene expression was analyzed by qPCR. Results: DKO mice had almost three-fold lower total cholesterol levels than DKO/hA-I and almost negligible HDL-cholesterol levels, which were strongly elevated in DKO/hA-I mice. In the aortic sinus, DKO developed plaques that were over 16 times larger than those in DKO/hA-I. In both genotypes, Abca1 gene expression peaked in the jejunum; the same trend was seen for Abcg5/Abcg8. Cd36 and Npc1l1 had similar expression levels along the length of the small intestine. Mttp expression was dramatically lower in the ileum, whereas that of Srebf2 and of the ileal sodium/bile acid cotransporter Slc10a2 peaked in the last portion of the small intestine. Despite their opposite phenotypes, the expression of all genes analyzed was not different between DKO and DKO/hA-I. Conclusions: Although different levels of apoA-I/HDL dramatically affect the plasma lipid profile and the atherosclerosis development, they did not seem to affect the expression of genes with a relevant role in intestinal lipid metabolism.