Flurbiprofen ameliorated obesity by attenuating leptin resistance induced by endoplasmic reticulum stress

被引：49

作者：

Hosoi, Toru ^{[1
]}

Yamaguchi, Rie ^{[1
]}

Noji, Kikuko ^{[1
]}

Matsuo, Suguru ^{[1
]}

Baba, Sachiko ^{[1
]}

Toyoda, Keisuke ^{[1
]}

Suezawa, Takahiro ^{[1
]}

Kayano, Takaaki ^{[1
]}

Tanaka, Shinpei ^{[2
]}

Ozawa, Koichiro ^{[1
]}

机构：

[1] Hiroshima Univ, Dept Pharmacotherapy, Grad Sch Biomed & Hlth Sci, Hiroshima, Japan

[2] Hiroshima Univ, Sch Integrated Arts & Sci, Higashihiroshima 724, Japan

来源：

EMBO MOLECULAR MEDICINE | 2014年 / 6卷 / 03期

关键词：

nonsteroidal anti-inflammatory drug; STAT3; aldehyde dehydrogenase; UNFOLDED PROTEIN RESPONSE; GENE-EXPRESSION; ER STRESS; ACTIVATION; AGGREGATION; IDENTIFICATION; APOPTOSIS; TARGET; STAT3; IRE1;

D O I：

10.1002/emmm.201303227

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

100103 [病原生物学]; 100218 [急诊医学];

摘要：

Endoplasmic reticulum (ER) stress, caused by the accumulation of unfolded proteins, is involved in the development of obesity. We demonstrated that flurbiprofen, a nonsteroidal anti-inflammatory drug (NSAID), exhibited chaperone activity, which reduced protein aggregation and alleviated ER stress-induced leptin resistance, characterized by insensitivity to the actions of the anti-obesity hormone leptin. This result was further supported by flurbiprofen attenuating high-fat diet-induced obesity in mice. The other NSAIDs tested did not exhibit such effects, which suggested that this anti-obesity action is mediated independent of NSAIDs. Using ferriteglycidyl methacrylate beads, we identified aldehyde dehydrogenase as the target of flurbiprofen, but not of the other NSAIDs. These results suggest that flurbiprofen may have unique pharmacological properties that reduce the accumulation of unfolded proteins and may represent a new class of drug for the fundamental treatment of obesity.

引用

页码：335 / 346

页数：12

共 48 条

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