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The cannabinoid receptor 1 and its role in influencing peripheral metabolism

Authors

  • L. O'Keefe,

    1. Biomedical and Lifestyle Disease Unit, College of Health and Biomedicine, Victoria University, Victoria, Australia
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  • A. C. Simcocks,

    1. Biomedical and Lifestyle Disease Unit, College of Health and Biomedicine, Victoria University, Victoria, Australia
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  • D. H. Hryciw,

    1. Department of Physiology, The University of Melbourne, Parkville, Australia
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  • M. L. Mathai,

    1. Biomedical and Lifestyle Disease Unit, College of Health and Biomedicine, Victoria University, Victoria, Australia
    2. The Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Parkville, Australia
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  • A. J. McAinch

    Corresponding author
    1. Biomedical and Lifestyle Disease Unit, College of Health and Biomedicine, Victoria University, Victoria, Australia
    • Correspondence to: Associate Prof Andrew J. McAinch, College of Health and Biomedicine, Victoria University, St Albans Campus, PO Box 14428, Melbourne, Vic 8001, Australia.E-mail: andrew.mcainch@vu.edu.au

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Abstract

Evidence from in vitro and in vivo studies has demonstrated the deleterious pathological effects of a dysregulated endocannabinoid system. Increased stimulation of the cannabinoid receptor 1 (CB1) and subsequent downstream cellular signalling are both causative in the deleterious pathological effects observed in a number of diseases. When the CB1 cell signalling cascade is blocked, this results in whole body weight-loss, leading to a reduction in obesity and associated co-morbidities. In the central nervous system; however, CB1 antagonism results in adverse psychological side effects. Blockade of CB1 via peripheral acting compounds that do not cross the blood–brain barrier have been determined to have beneficial effects in metabolic tissues such as the liver and skeletal muscle. These results support the notion that peripheral blockade of CB1 using pharmacological antagonists is a viable target for the treatment of the current epidemic of obesity and its associated co-morbidities.

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