Pemafibrate, a novel selective peroxisome proliferator-activated receptor alpha modulator, improves the pathogenesis in a rodent model of nonalcoholic steatohepatitis

被引：103

作者：

Honda, Yasushi ^{[1
]}

Kessoku, Takaomi ^{[1
]}

Ogawa, Yuji ^{[1
]}

Tomeno, Wataru ^{[1
]}

Imajo, Kento ^{[1
]}

Fujita, Koji ^{[1
]}

Yoneda, Masato ^{[1
]}

Takizawa, Toshiaki ^{[2
]}

Saito, Satoru ^{[1
]}

Nagashima, Yoji ^{[3
]}

Nakajima, Atsushi ^{[1
]}

机构：

[1] Yokohama City Univ, Grad Sch Med, Dept Gastroenterol & Hepatol, Yokohama, Kanagawa, Japan

[2] Kowa Co Ltd, Tokyo New Drug Res Labs, Dept Pharmacol Res, Tokyo, Japan

[3] Tokyo Womens Med Univ, Dept Surg Pathol, Tokyo, Japan

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

关键词：

FATTY LIVER-DISEASE; DE-NOVO EXPRESSION; PPAR-ALPHA; UNCOUPLING PROTEIN-3; HEPATIC STEATOSIS; LIPID-METABOLISM; CONTROLLED-TRIAL; GENE-EXPRESSION; SPPARM-ALPHA; MOUSE MODEL;

D O I：

10.1038/srep42477

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The efficacy of peroxisome proliferator-activated receptor alpha-agonists (e.g., fibrates) against nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) in humans is not known. Pemafibrate is a novel selective peroxisome proliferator-activated receptor a modulator that can maximize the beneficial effects and minimize the adverse effects of fibrates used currently. In a phase-2 study, pemafibrate was shown to improve liver dysfunction in patients with dyslipidaemia. In the present study, we first investigated the effect of pemafibrate on rodent models of NASH. Pemafibrate efficacy was assessed in a diet-induced rodent model of NASH compared with fenofibrate. Pemafibrate and fenofibrate improved obesity, dyslipidaemia, liver dysfunction, and the pathological condition of NASH. Pemafibrate improved insulin resistance and increased energy expenditure significantly. To investigate the effects of pemafibrate, we analysed the gene expressions and protein levels involved in lipid metabolism. We also analysed uncoupling protein 3 (UCP3) expression. Pemafibrate stimulated lipid turnover and upregulated UCP3 expression in the liver. Levels of acyl-CoA oxidase 1 and UCP3 protein were increased by pemafibrate significantly. Pemafibrate can improve the pathogenesis of NASH by modulation of lipid turnover and energy metabolism in the liver. Pemafibrate is a promising therapeutic agent for NAFLD/NASH.

引用

页数：11

共 63 条

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