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Glycobiology Advance Access published online on May 25, 2005
Glycobiology, doi:10.1093/glycob/cwi078
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© The Author 2005. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oupjournals.org
Received February 16, 2005
Revised May 9, 2005
Accepted May 15, 2005

Article

Dietary Ganglioside Decreases Cholesterol Content, Caveolin Expression and Inflammatory Mediators in Rat Intestinal Microdomains

Eek Joong Park 1, Miyoung Suh 1, Benjamin Thomson 1, Kalathur S. Ramanujam 2, Alan B.R. Thomson 3, and M. Thomas Clandinin 4*

1 Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada T6G 2P5
2 Wyeth Nutrition, University of Alberta, Edmonton, AB T6G 2P5, Canada
3 Department of Medicine, University of Alberta, Edmonton, Alberta, Canada T6G 2P5
4 Department of Agricultural, Food and Nutritional Science, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada T6G 2P5; Alberta Institute for Human Nutrition, University of Alberta, Edmonton, AB T6G 2P5, Canada

* To whom correspondence should be addressed.
M. Thomas Clandinin, E-mail: tom.clandinin{at}ualberta.ca


  Abstract

Background & Aims: Membrane microdomains rich in cholesterol and sphingolipids, including gangliosides, are known to be important regions for cell signaling and binding sites for various pathogens. Cholesterol depletion inhibits the cellular entry of pathogens and also reduces inflammatory signals by disrupting microdomain structure. Our previous study showed that 5 dietary gangliosides increased total ganglioside incorporation while decreasing cholesterol in the intestinal mucosa. We hypothesized that diet-induced reduction in cholesterol content in the intestinal mucosa disrupts microdomain structure resulting in reduced pro-inflammatory signals. Methods: Male weanling Sprague-Dawley rats were fed semi-purified diets for 2 weeks. Experimental diets were formulated to include either ganglioside-enriched lipid (GG 10 diet, 0.02% gangliosides (w/w of diet) or polyunsaturated fatty acid (PUFA diet, 1% arachidonic acid and 0.5% docosahexaenoic acid, w/w of total fat), in a control diet containing 20% fat. Levels of cholesterol, ganglioside, caveolin, platelet activating factor (PAF) and diglyceride (DG) were measured in the microdomain isolated from the intestinal brush border. Results: The GG diet increased total gangliosides by 50% with a relative increase in GD3 and a 15 relative decrease in GM3. Cholesterol content was also reduced by 23% in the intestinal microdomain. These changes resulted in a significant decrease in the ratio of cholesterol to ganglioside. The GG diet and the PUFA diet were both associated with reduction in caveolin, PAF, and DG content in microdomains, whereas no change occurred in the ganglioside profile of animals fed the PUFA diet. Conclusions: Dietary gangliosides decrease the 20 cholesterol/ganglioside ratio, caveolin, PAF and DG content in microdomains thus exerting a potential anti-inflammatory effect during gut development.

Keywords: gangliosides/intestine/lipid rafts/microdomains/sphingolipid.
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