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Horm Metab Res 2014; 46(08): 529-536
DOI: 10.1055/s-0034-1375653
Review
© Georg Thieme Verlag KG Stuttgart · New York

The Endocannabinoid System – Back to the Scene of Cardiometabolic Risk Factors Control?

C. J. M. Martins
1   Laboratory of Clinical and Experimental Pathophysiology (CLINEX), Rio de Janeiro State University (UERJ), Rio de Janeiro, RJ, Brazil
,
V. Genelhu
1   Laboratory of Clinical and Experimental Pathophysiology (CLINEX), Rio de Janeiro State University (UERJ), Rio de Janeiro, RJ, Brazil
2   Pro-Rector for Research and Postgraduate Education, UNIGRANRIO, Duque de Caxias, RJ, Brazil
,
V. Di Marzo
3   Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli NA, Italy
,
E. A. Francischetti
1   Laboratory of Clinical and Experimental Pathophysiology (CLINEX), Rio de Janeiro State University (UERJ), Rio de Janeiro, RJ, Brazil
2   Pro-Rector for Research and Postgraduate Education, UNIGRANRIO, Duque de Caxias, RJ, Brazil
› Author Affiliations
Further Information

Publication History

received 15 February 2014

accepted 23 April 2014

Publication Date:
27 May 2014 (online)

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Abstract

This review examines the impact of the endocannabinoid signaling system on metabolic and cardiovascular health and the new therapeutic strategies that selectively target dysfunctional endocannabinoid action in peripheral tissues, without causing the undesirable central nervous system effects that occurred with the first-generation of CB1 receptor blockers. We first review the components of the endocannabinoid system and the enzymes that synthesize and degrade the endocannabinoids, the critical role of the system in the homeostasis of energy balance, and its hedonic aspects related to the incentive and motivational value of food. Second, we describe the central and peripheral actions of the endocannabinoid system and its interactions with other biological modulators, such as ghrelin and leptin. Third, we summarize data from human clinical trials with the CB1 inverse agonist rimonabant, showing that the drug, although effective in increasing weight loss with accompanying improvements in the metabolic profile of the participants in the RIO (Rimonabant In Obesity) trials, was withdrawn from the market because of the risk of serious adverse events. Finally, we describe: 1) the development of new selective peripheral blockers that interrupt endocannabinoid action selectively in peripheral tissues and that have been suggested as an alternative approach to treat the metabolic consequences of obesity and related diseases, without undesirable central nervous system effects, and 2) the potential for inhibition of enzymes of synthesis, as well as the possible role of endocannabinoid congeners, with opposing effects as compared to CB1 receptor agonists, in the control of metabolic disorders.

Key words

endocannabinoid system - cardiometabolic risk factors - insulin resistance - obesity
 

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