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Journal of Lipid Research, Vol. 47, 1852-1858, August 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Antiobesity action of -polylysine, a potent inhibitor of pancreatic lipase

Takahiro Tsujita^1,*, Hiroe Takaichi^*, Takeshi Takaku^*, Shigeyuki Aoyama and Jun Hiraki

^* Bioscience, Integrated Center for Sciences, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan
Research and Development Section, Chisso Corporation, Kachidoki-3, Chuo-ku, Tokyo 104-8555, Japan

Published, JLR Papers in Press, May 24, 2006.

¹ To whom correspondence should be addressed. e-mail: tsujita{at}m.ehime-u.ac.jp

In vitro, -polylysine (EPL) strongly inhibited the hydrolysis of trioleoylglycerol emulsified with phosphatidylcholine (PC) and taurocholate by either pancreatic lipase or carboxylester lipase. The EPL concentration required for 50% inhibition of pancreatic lipase, 0.12 µM, was eight times lower than the concentration of orlistat required for the same effect. The 50% inhibition concentration by EPL was affected by emulsifier species: it was increased 150 times, 70 times, and 230 times on gum arabic, phosphatidylserine, and phosphatidic acid emulsion, respectively, compared with PC emulsion. The 50% inhibition concentration by orlistat was little changed by emulsifier species. Gel-filtration experiments suggested that EPL did not bind strongly to pancreatic lipase, whereas orlistat did. To test the effect of EPL on obesity, mice were fed a high-fat diet containing 0.1, 0.2, or 0.4% EPL. EPL prevented the high-fat diet-induced increase in body weight and weight of the liver and visceral adipose tissues (epididymal and retroperitoneal). EPL also decreased plasma triacylglycerol and plasma cholesterol concentrations and liver triacylglycerol content after they had been increased by the high-fat diet. The fecal weights of mice were increased by the high-fat diet containing EPL compared with the high-fat diet alone. Fecal lipid was also increased by the diet containing EPL. These data clearly show that EPL has an antiobesity function in mice fed a high-fat diet that acts by inhibiting intestinal absorption of dietary fat.

Supplementary key words orlistat • high-fat diet • obesity

Abbreviations: EPL, -polylysine; PA, phosphatidic acid; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PS, phosphatidylserine; TES, N-tris(hydroxylmethyl)-methyl-2-aminoethanesulfonic acid; TO, trioleoylglycerol

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