The role of the endocannabinoid system in the control of energy homeostasis

Abstract

The endocannabinoid system has recently emerged as an important regulator of energy homeostasis, involved in the control of both appetite and peripheral fat metabolism. We briefly review current understanding of the possible sites of action and cellular mechanisms involved in the central appetitive and peripheral metabolic effects of endocannabinoids. Studies in our laboratory, using leptin-deficient obese rodents and CB1 cannabinoid receptor (CB1)-deficient mice, have indicated that endocannabinoids acting via CB1 are involved in the hunger-induced increase in food intake and are negatively regulated by leptin in brain areas involved in appetite control, including the hypothalamus, limbic forebrain and amygdala. CB1 À/À mice are lean and are resistant to diet-induced obesity (DIO) despite similar energy intake to wild-type mice with DIO, suggesting that CB1 regulation of body weight involves additional peripheral targets. Such targets appear to include both adipose tissue and the liver. CB1 expressed in adipocytes has been implicated in the control of adiponectin secretion and lipoprotein lipase activity. Recent findings indicate that both endocannabinoids and CB1 are present in the liver and are upregulated in DIO. CB1 stimulation increases de novo hepatic lipogenesis through activation of the fatty acid biosynthetic pathway. Components of this pathway are also expressed in the hypothalamus where they have been implicated in the regulation of appetite. The fatty acid biosynthetic pathway may thus represent a common molecular target for the central appetitive and peripheral metabolic effects of endocannabinoids.

Are endocannabinoid type 1 receptor gene (CNR1) polymorphisms associated with obesity and metabolic syndrome in postmenopausal Polish women?

“…[4][5][6] A pharmacological blockade of endocannabinoid receptor 1 leads to weight loss and an improved metabolic risk profile in overweight and obese individuals. [13][14][15] Thus, it was hypothesized that genetic variation at the CNR1 locus could have an effect on adiposity.…”

“…2 The CB1 receptor, encoded by the CNR1 gene, has the greatest expression in the central nervous system but also in several peripheral organs including liver, muscle and adipose tissue. [3][4][5][6] Evidence suggests that CB1 and its endogenous ligands, the endocannabinoids, are involved in the regulation of energy balance, influencing feeding behavior and body weight. [4][5][6] The endocannabinoid receptor type 1 gene, CNR1, is located on 6q14-q15.…”

“…[3][4][5][6] Evidence suggests that CB1 and its endogenous ligands, the endocannabinoids, are involved in the regulation of energy balance, influencing feeding behavior and body weight. [4][5][6] The endocannabinoid receptor type 1 gene, CNR1, is located on 6q14-q15. Several human CNR1 polymorphisms have been recently described in the European-American, African-American and Japanese individuals in association with polysubstance abuse.…”

PUFA-derived endocannabinoids: an overview

“…Unfortunately, the mechanisms by which different fatty acids contribute to obesity are not well-understood yet and further research is needed. The involvement of the endocannabinoid system in obesity is supported by the following observations: (i) CB 1 receptor antagonists are significantly more efficacious in reducing caloric intake and body weight in rodents with diet-induced or genetic obesity than in their respective lean controls (95,98,99) ; (ii) CB 1 −/− mice are resistant to diet-induced obesity (100,101) ; and (iii) both an up-regulation of CB 1 receptors and elevated endocannabinoid levels have been detected in the adipose tissue of obese compared with lean patients (102,103) . Importantly, CB 1 receptor antagonists show significant anti-obesity effects.…”

The Endocannabinoid 2-Arachidonoyl-Glycerol Controls Odor Sensitivity in Larvae of Xenopus laevis

“…The endocannabinoid system is important for energy homeostasis and nutrition (Horvath, 2006;Osei-Hyiaman et al, 2006;Matias and Di Marzo, 2007). At the central stages of the nervous system, it has been well described that the endocannabinoid system plays a dual role in the regulation of food intake as well as in the homeostatic and nonhomeostatic (or hedonic) energy regulation (Matias et al, 2008).…”