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

Autor: Toru Hosoi, Rie Yamaguchi, Kikuko Noji, Suguru Matsuo, Sachiko Baba, Keisuke Toyoda, Takahiro Suezawa, Takaaki Kayano, Shinpei Tanaka, Koichiro Ozawa
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Zdroj: EMBO Molecular Medicine, Vol 6, Iss 3, Pp 335-346 (2014)
Druh dokumentu: article
ISSN: 1757-4676
1757-4684
DOI: 10.1002/emmm.201303227
Popis: Abstract 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.
Databáze: Directory of Open Access Journals
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