Flurbiprofen ameliorated obesity by attenuating leptin resistance induced by endoplasmic reticulum stress.
Flurbiprofen ameliorated obesity by attenuating leptin resistance induced by endoplasmic reticulum stress.
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弗拉伯利酮通过衰减内质网应激诱导的瘦素耐药性来改善肥胖症。
DOI：
10.1002/emmm.201303227
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发表时间：
2014-03
影响因子：
11.1
通讯作者：
Ozawa, Koichiro
中科院分区：
文献类型：
--
作者：
Hosoi, Toru;Yamaguchi, Rie;Noji, Kikuko;Matsuo, Suguru;Baba, Sachiko;Toyoda, Keisuke;Suezawa, Takahiro;Kayano, Takaaki;Tanaka, Shinpei;Ozawa, Koichiro
内质网（ER）应激，由未折叠蛋白质的积累引起，参与肥胖的发展。我们证明，氟比洛芬，非甾体抗炎药（NSAID），表现出伴侣活性，减少蛋白质聚集和减轻ER应激诱导的瘦素抵抗，其特征在于不敏感的抗肥胖激素瘦素的行动。氟比洛芬减轻小鼠高脂饮食诱导的肥胖进一步支持了这一结果。测试的其他NSAID没有表现出这种作用，这表明这种抗肥胖作用是独立于NSAID介导的。使用铁甲基丙烯酸缩水甘油酯珠，我们确定醛脱氢酶为目标的氟比洛芬，但不是其他非甾体抗炎药。这些结果表明，氟比洛芬可能具有独特的药理学特性，减少未折叠蛋白质的积累，并可能代表一类新的药物，用于肥胖的根本治疗。代谢;药理学与药物发现
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. Subject Categories Metabolism; Pharmacology & Drug Discovery
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