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Pharmaceuticals 2018, 11(2), 55; https://doi.org/10.3390/ph11020055

Endocannabinoids in Body Weight Control

Institute of Anatomy, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany
These authors contributed equally.
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Author to whom correspondence should be addressed.
Received: 28 April 2018 / Revised: 17 May 2018 / Accepted: 28 May 2018 / Published: 30 May 2018
(This article belongs to the Special Issue Cannabinoids as Medicines)
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Abstract

Maintenance of body weight is fundamental to maintain one’s health and to promote longevity. Nevertheless, it appears that the global obesity epidemic is still constantly increasing. Endocannabinoids (eCBs) are lipid messengers that are involved in overall body weight control by interfering with manifold central and peripheral regulatory circuits that orchestrate energy homeostasis. Initially, blocking of eCB signaling by first generation cannabinoid type 1 receptor (CB1) inverse agonists such as rimonabant revealed body weight-reducing effects in laboratory animals and men. Unfortunately, rimonabant also induced severe psychiatric side effects. At this point, it became clear that future cannabinoid research has to decipher more precisely the underlying central and peripheral mechanisms behind eCB-driven control of feeding behavior and whole body energy metabolism. Here, we will summarize the most recent advances in understanding how central eCBs interfere with circuits in the brain that control food intake and energy expenditure. Next, we will focus on how peripheral eCBs affect food digestion, nutrient transformation and energy expenditure by interfering with signaling cascades in the gastrointestinal tract, liver, pancreas, fat depots and endocrine glands. To finally outline the safe future potential of cannabinoids as medicines, our overall goal is to address the molecular, cellular and pharmacological logic behind central and peripheral eCB-mediated body weight control, and to figure out how these precise mechanistic insights are currently transferred into the development of next generation cannabinoid medicines displaying clearly improved safety profiles, such as significantly reduced side effects. View Full-Text
Keywords: body weight; obesity; anorexia; cancer cachexia; endocannabinoids; cannabinoid type 1 receptor; CB1; allosteric CB1 ligands body weight; obesity; anorexia; cancer cachexia; endocannabinoids; cannabinoid type 1 receptor; CB1; allosteric CB1 ligands
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Horn, H.; Böhme, B.; Dietrich, L.; Koch, M. Endocannabinoids in Body Weight Control. Pharmaceuticals 2018, 11, 55.

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