薬理と治療

Abstract

Backgroud TAK-085（Lotriga(R)）is a highly purified, concentrated n-3 fatty acid product primarily containing eicosapentaenoic acid ethyl ester （EPA-E）and docosahexaenoic acid ethyl ester （DHA-E）, used to treat hypertriglyceridemia. We investigated the triglyceride（TG）-lowering effects of TAK-085 in female Wistar fatty rats, an animal model for leptin receptor defects, obesity, and hyperlipidemia. Methods and Results After 16-days administration of TAK-085 in femal Wistar fatty rats, plasma lipid levels were determined. TAK-085（500 and 1500 mg╱kg）dose-dependently decreased plasma TG levels by 17％ and 33％, respectively. To investigate the mechanism of this, the hepatic production and plasma clearance of TGs were evaluated in Wistar fatty rats treated with TAK-085（1500 mg╱kg）. TAK-085 significantly increased plasma TG clearance after an intravenous injection of a TG emulsion. The half-life of TG clearance was shortened to about half by TAK-085 compared with the control. The hepatic TG secretion rate was assessed using plasma TG levels after an intravenous injection of LPL inhibitor, Triton WR-1339(R). TAK-085 significantly inhibited the TG secretion rate by 11％. We also found a reduction of hepatic fatty acid synthesis from 14C-acetic acid in TAK-085-treated rats. Conclusions TAK-085 shows plasma TG-lowering effects due to the suppression of hepatic fatty acid synthesis and inhibition of very-low-density lipoprotein（VLDL）secretion, alongside the stimulation of TG clearance in obese-hyperlipidemic female Wistar fatty rats.