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

Susan Galloway¹ , Menuka MS Pallebage-Gamarallage¹ , Ryusuke Takechi¹ , Le Jian¹ , Russell D Johnsen²^,3 , Satvinder S Dhaliwal¹ and John CL Mamo¹

¹School of Public Health and Australian Technology Network (ATN), Centre for Metabolic Fitness, Curtin University of Technology, Perth, Western Australia

²Australian Neuromuscular Research Institute, QEII Medical Centre, Perth, Western Australia

³Centre for Neuromuscular and Neurological Disorders, University of Western Australia

author email corresponding author email

Lipids in Health and Disease 2008, 7:15doi:10.1186/1476-511X-7-15


Published:	22 April 2008

Abstract

Background

Amyloid-β (Aβ), 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 Aβ abundance whereas fasting abolishes expression. Apolipoprotein (apo) E has been shown to directly modulate Aβ 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 Aβ as a consequence of differences in lipid absorption. This study compared Aβ 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 Aβ abundance in small intestinal enterocytes. Apo E KO mice given the low-fat diet had similar enterocytic Aβ abundance compared to WT controls.

Results

The saturated fat diet substantially increased enterocytic Aβ 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 Aβ. Apo E may influence enterocytic lipid availability by modulating absorptive capacity.