Abstract:
:Adipocyte fatty-acid-binding protein, aP2 (FABP4) is expressed in adipocytes and macrophages, and integrates inflammatory and metabolic responses. Studies in aP2-deficient mice have shown that this lipid chaperone has a significant role in several aspects of metabolic syndrome, including type 2 diabetes and atherosclerosis. Here we demonstrate that an orally active small-molecule inhibitor of aP2 is an effective therapeutic agent against severe atherosclerosis and type 2 diabetes in mouse models. In macrophage and adipocyte cell lines with or without aP2, we also show the target specificity of this chemical intervention and its mechanisms of action on metabolic and inflammatory pathways. Our findings demonstrate that targeting aP2 with small-molecule inhibitors is possible and can lead to a new class of powerful therapeutic agents to prevent and treat metabolic diseases such as type 2 diabetes and atherosclerosis.
journal_name
Naturejournal_title
Natureauthors
Furuhashi M,Tuncman G,Görgün CZ,Makowski L,Atsumi G,Vaillancourt E,Kono K,Babaev VR,Fazio S,Linton MF,Sulsky R,Robl JA,Parker RA,Hotamisligil GSdoi
10.1038/nature05844subject
Has Abstractpub_date
2007-06-21 00:00:00pages
959-65issue
7147eissn
0028-0836issn
1476-4687pii
nature05844journal_volume
447pub_type
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