J. Lipid Res. Neurobiology of Lipids (ISSN1683-5506)
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A more recent version of this article appeared on August 1, 2006

Papers In Press, published online ahead of print May 24, 2006
J. Lipid Res., doi:10.1194/jlr.M600168-JLR200
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Submitted on April 12, 2006
Revised on May 24, 2006
Accepted on May 24, 2006

Anti-obese action of epsilon -polylysine, a potent inhibitor of pancreatic lipase

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

Bioscience, Integrated Center for Sciences, Ehime University, Toon, Ehime 791-0295

Corresponding Author: tsujita{at}m.ehime-u.ac.jp

In vitro, e-polylysine (EPL) strongly inhibited the hydrolysis of trioleoylglycerol (TO) 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 8 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 approximately 150 times, 70 times and 230 times on arabic gum, phosphatidylserine (PS) and phosphatidic acid (PA) emulsion, respectively, when compared with PC emulsion. The 50% inhibition concentration by orlistat was little changed by emulsifier species. Gel-filtration experiments suggested 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 elevation in body weight and weight of the liver and visceral adipose tissues (epididymal and retroperitoneal). EPL also decreased the plasma triacylglycerol and plasma cholesterol concentration, 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 when compared to the high-fat diet alone. Fecal lipid was also increased by the diet containing EPL. These data clearly show that EPL has an anti-obesity function in mice fed a high-fat diet through inhibiting intestinal absorption of dietary fat.


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