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Glycobiology Advance Access originally published online on May 25, 2005
Glycobiology 2005 15(10):935-942; 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

Dietary ganglioside decreases cholesterol content, caveolin expression and inflammatory mediators in rat intestinal microdomains

Eek Joong Park3, Miyoung Suh2,3, Benjamin Thomson3, Alan B.R. Thomson4, Kalathur S. Ramanujam5 and M. Thomas Clinin1,4,6

3 Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada T6G 2P5; 4 Department of Medicine, University of Alberta, Edmonton, Alberta, Canada T6G 2P5; 5 Wyeth Nutrition, Collegeville, PA; and 6 Alberta Institute for Human Nutrition, University of Alberta, Edmonton, Alberta, Canada T6G 2P5

1 To whom correspondence should be addressed; e-mail: tom.clandinin{at}ualberta.ca

2 Present address: Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada R3T 2N2

Received on February 16, 2005; revised on May 9, 2005; accepted on May 15, 2005

Membrane microdomains rich in cholesterol and sphingolipids, including gangliosides (GGs), 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 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. Male weanling Sprague-Dawley rats were fed semipurified diets for 2 weeks. Experimental diets were formulated to include either ganglioside-enriched lipid (GG 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, GG, caveolin, platelet activating factor (PAF), and diglyceride (DG) were measured in the microdomain isolated from the intestinal brush border. The GG diet increased total gangliosides by 50% with a relative increase in GD3 and a 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. Dietary gangliosides decrease the cholesterol/ganglioside ratio, caveolin, PAF and DG content in microdomains thus exerting a potential anti-inflammatory effect during gut development.

Key words: gangliosides / intestine / lipid rafts / microdomains / sphingolipid

Ganglioside nomenclature is described by Svennerholm (1964) and the IUPAC-IUB (1977) recommendation.


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