Synergistic effects of high fat feeding and apolipoprotein E deletion on enterocytic amyloid-beta abundance

Background: Amyloid-beta (A beta), a key protein found in amyloid plaques of subjects with Alzheimer's disease is expressed in the absorptive epithelial cells of the small intestine. Ingestion of saturated fat significantly enhances enterocytic A beta abundance whereas fasting abolishes expression. Apolipoprotein (apo) E has been shown to directly modulate A beta biogenesis in liver and neuronal cells but it's effect in enterocytes is not known. In addition, apo E modulates villi length, which may indirectly modulate A beta as a consequence of differences in lipid absorption. This study compared A beta abundance and villi length in wild-type (WT) and apo E knockout (KO) mice maintained on either a low-fat or high-fat diet. Wild-type C57BL/6J and apo E KO mice were randomised for six-months to a diet containing either 4% (w/w) unsaturated fats, or chow comprising 16% saturated fats and 1% cholesterol. Quantitative immunohistochemistry was used to assess A beta abundance in small intestinal enterocytes. Apo E KO mice given the low-fat diet had similar enterocytic A beta abundance compared to WT controls. Results: The saturated fat diet substantially increased enterocytic A beta in WT and in apo E KO mice, however the effect was greater in the latter. Villi height was significantly greater in apo E KO mice than for WT controls when given the low-fat diet. However, WT mice had comparable villi length to apo E KO when fed the saturated fat and cholesterol enriched diet. There was no effect of the high-fat diet on villi length in apo E KO mice. Conclusion: The findings of this study are consistent with the notion that lipid substrate availability modulates enterocytic A beta. Apo E may influence enterocytic lipid availability by modulating absorptive capacity.