OBJECTIVE: Chondroitin sulfate is an acidic polymer consisting of repeating D-glucuronic acid and D-N-acetylgalactosamine units, and the N-acetylgalactosamine is substituted with the sulfate at either the 4 H or 6 H position, with approximately one sulfate being present per disaccharide unit. The present study assessed the effects of chondroitin sulfate on the activity of pancreatic lipase and lipid uptake into brush border membrane vesicles of the rat small intestine in vitro, and on the degree of fat storage induced in mice by the oral administration of a high-fat diet for 8 weeks. DESIGN AND MEASUREMENTS: Experiments were carried out to clarify whether or not chondroitin sulfate inhibited pancreatic lipase activity in assay systems using triolein emulsi®ed with phosphatidylcholine or gum arabic. In addition, the effects of chondroitin sulfate on lipid absorption by brush border membrane vesicles were examined. Moreover, mice were fed a high-fat diet and treated with chondroitin sulfate for 8 weeks. RESULTS: Chondroitin sulfate dose-dependently inhibited the pancreatic lipase activity in an assay system using triolein emulsi®ed with phosphatidylcholine. In addition, chondroitin sulfate inhibited the palmitic acid uptake into the brush border membrane vesicles of the rat jejunum. Chondroitin sulfate caused the reduction of body weight and parametrial adipose tissue weight, and prevention of fatty liver and hyperlipidemia in mice fed a high-fat diet. CONCLUSION: The reduction of fat storage and the antihyperlipidemic action of chondroitin sulfate might be due to the inhibition of small intestinal absorption of dietary fat through the inhibition of pancreatic lipase activity and fatty acid uptake through brush border membrane.

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