Synergistic effects of high fat feeding and apolipoprotein E deletion on enterocytic amyloid-beta abundance.
BACKGROUND
Amyloid-beta (Abeta), 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 Abeta abundance whereas fasting abolishes expression. Apolipoprotein (apo) E has been shown to directly modulate Abeta 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 Abeta as a consequence of differences in lipid absorption. This study compared Abeta 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 Abeta abundance in small intestinal enterocytes. Apo E KO mice given the low-fat diet had similar enterocytic Abeta abundance compared to WT controls.


RESULTS
The saturated fat diet substantially increased enterocytic Abeta 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.


CONCLUSIONS
The findings of this study are consistent with the notion that lipid substrate availability modulates enterocytic Abeta. Apo E may influence enterocytic lipid availability by modulating absorptive capacity.
Galloway
Susan
S
School of Public Health and Australian Technology Network (ATN), Centre for Metabolic Fitness, Curtin University of Technology, Perth, Western Australia. susan.galloway@postgrad.curtin.edu.au
Pallebage-Gamarallage
Menuka M S
MM
Takechi
Ryusuke
R
Jian
Le
L
Johnsen
Russell D
RD
Dhaliwal
Satvinder S
SS
Mamo
John C L
JC
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics*; D004041:Dietary Fats / Q000378:metabolism*; D020895:Enterocytes / Q000378:metabolism*; D005260:Female; D006937:Hypercholesterolemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007408:Intestinal Absorption / Q000235:genetics; D007421:Intestine, Small / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011897:Random Allocation; D015854:Up-Regulation / Q000235:genetics / Q000502:physiology
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D004041:Dietary Fats