國家衛生研究院 NHRI:Item 3990099045/8545
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    题名: A novel peripheral cannabinoid receptor 1 antagonist, BPR0912, reduces weight independently of food intake and modulates thermogenesis
    作者: Hsiao, WC;Shia, KS;Wang, YT;Yeh, YN;Chang, CP;Lin, Y;Chen, PH;Wu, CH;Chao, YS;Hung, MS
    贡献者: Institute of Biotechnology and Pharmaceutical Research
    摘要: AIM: BPR0912 is a novel and potent peripheral CB1R antagonist. This study investigated the in vivo metabolic effects of BPR0912 treatment on both normal mice and diet-induced obese (DIO) mice. MATERIALS AND METHODS: The acute peripheral effects of BPR0912 administration on gastrointestinal transit and energy metabolism in normal mice were investigated. The effects of chronic BPR0912 treatment were compared to those of rimonabant using DIO mice. Alterations to body weight and biochemical and metabolic parameters were determined. RESULTS: Acute treatment with BPR0912 did not alter food intake or energy metabolism but efficiently reversed CB1R-mediated gastrointestinal delay. Chronic treatment of DIO mice with BPR0912 revealed that BPR0912 exerts a food intake-independent mechanism which contributes to weight loss. Genes involved in beta-oxidation and thermogenesis were up-regulated in WAT in addition to increased lipolytic activity, whereas Ucp1 expression was induced in BAT and body temperature was elevated. Expression of the beta2-adrenoceptor was specifically elevated in both WAT and BAT in a manner dependent on the BPR0912 dose. Lastly, chronic BPR0912 treatment was more efficacious than rimonabant in reducing hepatic triglycerides in DIO mice. CONCLUSION: BPR0912 exhibits significant in vivo efficacy in inducing food intake-independent weight loss in DIO mice while tending to reduce their hepatic steatosis. The thermogenic effects of BPR0912, as well as its modulation of protein and gene expression patterns in WAT and BAT, may enhance its efficacy as an anti-obesity agent. The results of our study support the benefits of the use of peripheral CB1R antagonists to combat metabolic disorders.
    日期: 2015-05
    關聯: Diabetes, Obesity and Metabolism. 2015 May;17(5):495-504.
    Link to: http://dx.doi.org/10.1111/dom.12447
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1462-8902&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000352255000008
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84926226439
    显示于类别:[洪明秀] 期刊論文
    [趙宇生(2002-2013)] 期刊論文
    [夏克山] 期刊論文
    [張竣評] 期刊論文

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