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Dysregulation of the endocannabinoid system in obesity.

Abstract

An activation of the endocannabinoid system (ECS) in obesity with increased concentrations of endocannabinoids in several tissues and in the circulation is described in this review. This increased availability of endocannabinoids might stimulate cannabinoid receptors in a pathophysiological manner. The successful use of the cannabinoid receptor CB(1) inverse agonists rimonabant and taranabant for weight loss and the treatment of obesity-associated metabolic disorders might well be through blocking this overstimulation of cannabinoid receptors. At present, no single mechanism has been identified that explains the increased bioavailability of endocannabinoids in obesity. Both increased synthesis and decreased degradation appear to operate in a species- and tissue-dependent manner, but many pieces of the puzzle still need to be collected. For example, most data show decreased fatty acid amide hydrolase (FAAH) expression and/or activity as a result of obesity or high-fat intake, but the endocannabinoid predominantly increased in tissues is 2-arachidonoylglycerol (2-AG), which is not degraded by FAAH in vivo. Furthermore, the influence of dietary fatty acids on the synthesis of endocannabinoids needs to be studied in much more detail. Although weight loss does not seem to influence activation of the endocannabinoid system (ECS) in human obesity, suggesting an underlying mechanisms independent of body weight, no such mechanism at the genetic level has yet been identified either. Thus, activation of the ECS is a hallmark of abdominal obesity, and explains the success of pharmacological CB(1) blockade, but serious attempts have to be made to clarify the underlying mechanisms of this activation.

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  • Publisher Full Text
  • Authors+Show Affiliations

    Franz Volhard Clinical Research Center, Medical Faculty of the Charité, Berlin, Germany. stefan.engeli@charite.de

    Source

    Journal of neuroendocrinology 20 Suppl 1: 2008 May pg 110-5

    MeSH

    Adipose Tissue
    Animals
    Brain
    Cannabinoid Receptor Modulators
    Diet
    Dietary Fats, Unsaturated
    Disease Models, Animal
    Endocannabinoids
    Humans
    Leptin
    Liver
    Obesity
    Pancreas
    Receptors, Cannabinoid
    Weight Loss

    Pub Type(s)

    Journal Article
    Review

    Language

    eng

    PubMed ID

    18426509

    Citation

    Engeli, S. "Dysregulation of the Endocannabinoid System in Obesity." Journal of Neuroendocrinology, vol. 20 Suppl 1, 2008, pp. 110-5.
    Engeli S. Dysregulation of the endocannabinoid system in obesity. J Neuroendocrinol. 2008;20 Suppl 1:110-5.
    Engeli, S. (2008). Dysregulation of the endocannabinoid system in obesity. Journal of Neuroendocrinology, 20 Suppl 1, pp. 110-5. doi:10.1111/j.1365-2826.2008.01683.x.
    Engeli S. Dysregulation of the Endocannabinoid System in Obesity. J Neuroendocrinol. 2008;20 Suppl 1:110-5. PubMed PMID: 18426509.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Dysregulation of the endocannabinoid system in obesity. A1 - Engeli,S, PY - 2008/5/9/pubmed PY - 2008/7/19/medline PY - 2008/5/9/entrez SP - 110 EP - 5 JF - Journal of neuroendocrinology JO - J. Neuroendocrinol. VL - 20 Suppl 1 N2 - An activation of the endocannabinoid system (ECS) in obesity with increased concentrations of endocannabinoids in several tissues and in the circulation is described in this review. This increased availability of endocannabinoids might stimulate cannabinoid receptors in a pathophysiological manner. The successful use of the cannabinoid receptor CB(1) inverse agonists rimonabant and taranabant for weight loss and the treatment of obesity-associated metabolic disorders might well be through blocking this overstimulation of cannabinoid receptors. At present, no single mechanism has been identified that explains the increased bioavailability of endocannabinoids in obesity. Both increased synthesis and decreased degradation appear to operate in a species- and tissue-dependent manner, but many pieces of the puzzle still need to be collected. For example, most data show decreased fatty acid amide hydrolase (FAAH) expression and/or activity as a result of obesity or high-fat intake, but the endocannabinoid predominantly increased in tissues is 2-arachidonoylglycerol (2-AG), which is not degraded by FAAH in vivo. Furthermore, the influence of dietary fatty acids on the synthesis of endocannabinoids needs to be studied in much more detail. Although weight loss does not seem to influence activation of the endocannabinoid system (ECS) in human obesity, suggesting an underlying mechanisms independent of body weight, no such mechanism at the genetic level has yet been identified either. Thus, activation of the ECS is a hallmark of abdominal obesity, and explains the success of pharmacological CB(1) blockade, but serious attempts have to be made to clarify the underlying mechanisms of this activation. SN - 1365-2826 UR - https://www.unboundmedicine.com/medline/citation/18426509/Dysregulation_of_the_endocannabinoid_system_in_obesity_ L2 - https://doi.org/10.1111/j.1365-2826.2008.01683.x DB - PRIME DP - Unbound Medicine ER -