Expression of Cannabinoid CB1 Receptors by Vagal Afferent Neurons Is Inhibited by Cholecystokinin

Burdyga, Galina; Lal, Simon; Varró, Andrea; Dimaline, R.; Thompson, David G.; Dockray, Graham J.

doi:10.1523/jneurosci.5404-03.2004

Cited by 251 publications

(239 citation statements)

References 47 publications

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“…Based on the co-localization of CCK1R and CB1R in vagal nerves and the observation that CCK agonist or antagonist can affect the expression level of CB1R in vagal afferent neurons, 70 it has been hypothesized that CB1R inverse agonist may affect satiety. 71 However, the co-localization per se does not necessarily support a satiety effect.…”

Section: Do Cb1r Agents Produce Weight Loss-independent Effects?mentioning

confidence: 99%

Cannabinoid-1 receptor inverse agonists: current understanding of mechanism of action and unanswered questions

Fong

Heymsfield

2009

Int J Obes

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Rimonabant and taranabant are two extensively studied cannabinoid-1 receptor (CB1R) inverse agonists. Their effects on in vivo peripheral tissue metabolism are generally well replicated. The central nervous system site of action of taranabant or rimonabant is firmly established based on brain receptor occupancy studies. At the whole-body level, the mechanism of action of CB1R inverse agonists includes a reduction in food intake and an increase in energy expenditure. At the tissue level, fat mass reduction, liver lipid reduction and improved insulin sensitivity have been shown. These effects on tissue metabolism are readily explained by CB1R inverse agonist acting on brain CB1R and indirectly influencing the tissue metabolism through the autonomic nervous system. It has also been hypothesized that rimonabant acts directly on adipocytes, hepatocytes, pancreatic islets or skeletal muscle in addition to acting on brain CB1R, although strong support for the contribution of peripherally located CB1R to in vivo efficacy is still lacking. This review will carefully examine the published literature and provide a perspective on what new tools and studies are required to address the peripheral site of action hypothesis.

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Section: Do Cb1r Agents Produce Weight Loss-independent Effects?mentioning

confidence: 99%

Cannabinoid-1 receptor inverse agonists: current understanding of mechanism of action and unanswered questions

Fong

Heymsfield

2009

Int J Obes

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“…Such an 'indirect' pathway is compatible with recent findings that CB1 mRNA is present in cholecystokinin (CCK)-containing neurons in the nodose ganglion, where CB1 mRNA expression is upregulated by fasting and downregulated by refeeding. 32 This latter effect could be mimicked by the satiety hormone CCK, which may thus suppress feeding indirectly via reducing orexigenic signaling via CB1. 32 Endocannabinoids and CB1 receptors are integral components of the mesolimbic reward pathway, 33 and cannabinoids are known to increase the taste for palatable food.…”

Section: Endocannabinoid Regulation Of Appetitive Behaviormentioning

confidence: 99%

“…32 This latter effect could be mimicked by the satiety hormone CCK, which may thus suppress feeding indirectly via reducing orexigenic signaling via CB1. 32 Endocannabinoids and CB1 receptors are integral components of the mesolimbic reward pathway, 33 and cannabinoids are known to increase the taste for palatable food. 14,34 Not surprisingly then, sites in the limbic forebrain have also been implicated in their orexigenic effects.…”

Section: Endocannabinoid Regulation Of Appetitive Behaviormentioning

confidence: 99%

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

et al. 2006

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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.

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“…25 Therefore, the activation of CB1 on nerve terminals innervating the gastrointestinal tract may be involved in mediating satiety signals originating in the gut and the endocannabinoid system may also influence food intake by a gastroduodenal cross-talk with CCK signaling. 25 In support of this hypothesis, endocannabinoid levels in the gastrointestinal tract are regulated by the feeding state. In fact, starvation induces a seven-fold increase in the levels of anandamide in the small intestine, an effect that is reversed by refeeding.…”

Section: Endocannabinoid System and Peripheral Organsmentioning

confidence: 99%

How many sites of action for endocannabinoids to control energy metabolism?

et al. 2006

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The promising results obtained by clinical trials using Rimonabant to tackle visceral obesity and related disorders recently promoted a remarkable impulse to carry out detailed investigations into the mechanisms of action of endocannabinoids in regulating food intake and energy metabolism. The endocannabinoid system has been known for many years to play an important role in the modulation of the neuronal pathways mediating the rewarding properties of food. However, in the last few years, with the advanced understanding of the crucial role of the hypothalamic neuronal network in the regulation of appetite, several studies have also directed attention to the orexigenic role of the endocannabinoid system, substantiating the well known appetite stimulating properties of derivatives of Cannabis sativa. Furthermore, the last 2 years have seen a number of relevant publications emphasizing the role of endocannabinoids as significant players in various peripheral metabolic processes. To date, the roles of the endocannabinoid system in influencing energy metabolism have proved to be more complex than was formerly believed. However, the diverse ability to modulate both central and peripheral processes highlights the pivotal involvement of the endocannabinoid system in the control of metabolic processes. This review describes the roles of endocannabinoids and the cannabinoid type 1 receptor (CB1) in the control of energy balance.

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Expression of Cannabinoid CB1 Receptors by Vagal Afferent Neurons Is Inhibited by Cholecystokinin

Cited by 251 publications

References 47 publications

Cannabinoid-1 receptor inverse agonists: current understanding of mechanism of action and unanswered questions

Cannabinoid-1 receptor inverse agonists: current understanding of mechanism of action and unanswered questions

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

How many sites of action for endocannabinoids to control energy metabolism?

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