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This table offers a comprehensive summary
illustration of how many cardiometabolic risk factors may be affected by the
ECS. In the brain, the hypothalamus receives and integrates signals
regarding the status of body-fat stores from adipose tissue and other
peripheral tissues. CB1-R overactivity in the hypothalamus is associated
with excess adiposity. CB1-R activation in the hypothalamus also sustains
overeating in obese animals. Endocannabinoids have been documented in
adipose tissue, with CB1-R having been shown to be active in stimulating
lipogenesis. Ongoing investigation in animals indicates that, in skeletal
muscle, CB1-R stimulation reduces insulin-mediated glucose uptake. In the
liver, it has been demonstrated that endocannabinoid-mediated increase in de
novo lipogenesis in the liver is a critical component in diet-induced
obesity. In the gastrointestinal tract, it is known that CB1-R activation by
anandamide increases food intake. A surge in intestinal anandamide levels
serves as a short-range hunger signal to promote feeding. Badman MK, Flier JS. The gut and energy balance: visceral allies in the obesity wars. Science. 2005;307:1909-1914. Schwartz GJ. The role of gastrointestinal vagal afferents in the control of food intake: Current Prospects. Nutrition. 2000;16:866-873. Bensaid M, Gary-Bobo M, Esclangon A, et al. The cannabinoid CB1 receptor antagonist SR141716 increases Acrp30 mRNA expression in adipose tissue of obese fa/fa rats and in cultured adipocyte cells. Mol Pharmacol. 2003;63:908-914. Di Marzo V, Goparaju SK, Wang L, et al. Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature. 2001;410:822-825. Cota D, Marsicano G, Tschöp M, et al. The endogenous cannabinoid system affects energy balance via central orexigenic drive and peripheral lipogenesis. J Clin Invest. 2003;112:423-431. Pagotto U, Vicennati V, Pasquali R. The endocannabinoid system and the treatment of obesity. Ann Med. 2005;37:270-275. Liu YL, Connoley IP, Wilson CA, Stock MJ. Effects of the cannabinoid CB1 receptor antagonist SR141716 on oxygen consumption and soleus muscle glucose uptake in Lep(ob)/Lep(ob) mice. Int J Obes (Lond). 2005;29:183-187. Osei-Hyiaman D, DePetrillo M, Pacher P, et al. Endocannabinoid activation at hepatic CB1 receptors stimulates fatty acid synthesis and contributes to diet-induced obesity. J Clin Invest. 2005;115:1298-1305. Gomez RG, Navarro M, Ferrer B, et al. A peripheral mechanism for CB1 cannabinoid receptor-dependent modulation of feeding. J. Neurosci. 2002;22:9612-9617. |