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2018 ; 11
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): ä Nephropedia Template TP
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Endocannabinoids in Body Weight Control
#MMPMID29849009
Horn H
; Böhme B
; Dietrich L
; Koch M
Pharmaceuticals (Basel)
2018[May]; 11
(2
): ä PMID29849009
show ga
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.