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The therapeutic potential of targeting the peripheral endocannabinoid/CB1 receptor system

  • Joseph Tam
    Correspondence
    Corresponding author at: Obesity and Metabolism Laboratory, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, POB 12065, Jerusalem 9112001, Israel.
    Affiliations
    Obesity and Metabolism Laboratory, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel
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  • Liad Hinden
    Affiliations
    Obesity and Metabolism Laboratory, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel
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  • Adi Drori
    Affiliations
    Obesity and Metabolism Laboratory, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel
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  • Shiran Udi
    Affiliations
    Obesity and Metabolism Laboratory, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel
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  • Shahar Azar
    Affiliations
    Obesity and Metabolism Laboratory, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel
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  • Saja Baraghithy
    Affiliations
    Obesity and Metabolism Laboratory, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel
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Published:January 11, 2018DOI:https://doi.org/10.1016/j.ejim.2018.01.009

      Highlights

      • CB1 receptor modulates energy homeostasis via both central and peripheral mechanisms.
      • Blockade of CB1 receptor in periphery ameliorates the development of visceral obesity.
      • Hepatic CB1 receptor regulates lipogenesis and fatty acid oxidation in the liver.
      • Activating renal CB1 receptor promotes the development of chronic kidney diseases.
      • Modulating skeletal CB1 receptor may be beneficial in a range of skeletal disorders.

      Abstract

      Endocannabinoids (eCBs) are internal lipid mediators recognized by the cannabinoid-1 and -2 receptors (CB1R and CB2R, respectively), which also mediate the different physiological effects of marijuana. The endocannabinoid system, consisting of eCBs, their receptors, and the enzymes involved in their biosynthesis and degradation, is present in a vast number of peripheral organs. In this review we describe the role of the eCB/CB1R system in modulating the metabolism in several peripheral organs. We assess how eCBs, via activating the CB1R, contribute to obesity and regulate food intake. In addition, we describe their roles in modulating liver and kidney functions, as well as bone remodeling and mass. Special importance is given to emphasizing the efficacy of the recently developed peripherally restricted CB1R antagonists, which were pre-clinically tested in the management of energy homeostasis, and in ameliorating both obesity- and diabetes-induced metabolic complications.

      Keywords

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