The endogenous cannabinoid system affects energy balance via central orexigenic drive and peripheral lipogenesis.

  title={The endogenous cannabinoid system affects energy balance via central orexigenic drive and peripheral lipogenesis.},
  author={Daniela Cota and Giovanni Marsicano and Matthias H. Tsch{\"o}p and Yvonne Gr{\"u}bler and Cornelia Flachskamm and Mirjam I Schubert and D. R. Auer and Alexander Yassouridis and Christa Th{\"o}ne-Reineke and Sylvia Ortmann and Federica Tomassoni and Cristina Cervino and Enzo Nisoli and Astrid C. E. Linthorst and Renato Pasquali and Beat Lutz and G{\"u}nter K. Stalla and Uberto Pagotto},
  journal={The Journal of clinical investigation},
  volume={112 3},
The cannabinoid receptor type 1 (CB1) and its endogenous ligands, the endocannabinoids, are involved in the regulation of food intake. Here we show that the lack of CB1 in mice with a disrupted CB1 gene causes hypophagia and leanness. As compared with WT (CB1+/+) littermates, mice lacking CB1 (CB1-/-) exhibited reduced spontaneous caloric intake and, as a consequence of reduced total fat mass, decreased body weight. In young CB1-/- mice, the lean phenotype is predominantly caused by decreased… 

Figures and Tables from this paper

Hypothalamic CB1 cannabinoid receptors regulate energy balance in mice.

Findings suggest that hypothalamic CB(1) receptor signaling is a key determinant of energy expenditure under basal conditions and reveal its specific role in conveying the effects of leptin and pharmacological CB1 receptor antagonism on food intake.

Central and peripheral cannabinoid receptors as therapeutic targets in the control of food intake and body weight.

  • S. Engeli
  • Biology, Medicine
    Handbook of experimental pharmacology
  • 2012
Animal studies clarified the important role of CB1 receptors in the hypothalamus and in the limbic system in mediating orexigenic effects and demonstrated that CB1 inhibition protects against weight gain induced by high-fat feeding and reduces body weight in obese animals and humans.

Cannabinoid type 1 (CB1) receptors on Sim1-expressing neurons regulate energy expenditure in male mice.

Findings reveal a diet-dependent dissociation in the CB1 receptor control of food intake and EE, likely mediated by the PVN, where CB1 receptors on Sim1-positive neurons do not impact food intake but hinder EE during dietary environmental challenges that promote body weight gain.

Expression of the cannabinoid system in muscle: effects of a high-fat diet and CB1 receptor blockade.

The results of the present study indicate a diet-sensitive ECS in skeletal muscle, suggesting that blockade of CB1 receptors could work towards restoration of the metabolic adaption imposed by diet.

Deficiency of CB2 cannabinoid receptor in mice improves insulin sensitivity but increases food intake and obesity with age

These results indicate that the lack of CB2R-mediated responses protected mice from both age-related and diet-induced insulin resistance, suggesting that these receptors may be a potential therapeutic target in obesity and insulin resistance.

Peripheral cannabinoid-1 receptor blockade restores hypothalamic leptin signaling

Endocannabinoid system and its role in energy regulation

Dysregulation of the endocannabinoid system might contribute to the development of eating disorders and explain why CB1 receptor blockers are efficacious at reducing not only food intake but also the metabolic consequences of visceral adiposity and obesity.

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

Research in the laboratory has 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, suggesting that CB1 regulation of body weight involves additional peripheral targets.

Lack of Hypophagia in CB1 Null Mice is Associated to Decreased Hypothalamic POMC and CART Expression

Evidence suggests that a lack of hypophagia is associated with the suppression of ARC anorexigenic neuropeptides and that behavioral changes in food intake after constitutive CB1 ablation are likely mediated by impaired melanocortin and CART signaling in the hypothalamus.



Leptin-regulated endocannabinoids are involved in maintaining food intake

It is shown that following temporary food restriction, CB1 receptor knockout mice eat less than their wild-type littermates, and the CB1 antagonist SR141716A reduces food intake in wild- type but not knockout mice, which indicates that endocannabinoids in the hypothalamus may tonically activate CB1 receptors to maintain food intake and form part of the neural circuitry regulated by leptin.

Anandamide induces overeating: mediation by central cannabinoid (CB1) receptors

This first demonstration of anandamide-induced, CB1-mediated, overeating provides important evidence for the involvement of a central cannabinoid system in the normal control of eating.

Neither Agouti-Related Protein nor Neuropeptide Y Is Critically Required for the Regulation of Energy Homeostasis in Mice

The results demonstrate that neither AgRP nor NPY is a critically required orexigenic factor, suggesting that other pathways capable of regulating energy homeostasis can compensate for the loss of both AgRP and NPY.

Anti-obesity effect of SR141716, a CB1 receptor antagonist, in diet-induced obese mice.

It is suggested that SR141716 has a potential as a novel anti-obesity treatment and may influence metabolic processes as the body weight loss of SR 141716-treated mice was significantly higher during 24-h fasting compared with vehicle-treated animals, and when a 3-day treatment was compared with a pair feeding.

Inactivation of the mouse melanocortin-3 receptor results in increased fat mass and reduced lean body mass

Mc3r and Mc4r serve non-redundant roles in the regulation of energy homeostasis by studying Mc3r-deficient mice and comparing their functions in mice deficient for both genes.

Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice.

Most, but not all, CNS effects of Delta9-THC are mediated by the CB1 receptor, which accounts for the abuse potential of cannabis, while other effects such as analgesia suggest potential medicinal applications.

Absence of cocaine- and amphetamine-regulated transcript results in obesity in mice fed a high caloric diet.

It is shown that CART deficiency predisposed mice to become obese on a calorically dense diet, and CART may not be a major anorectic signal compared with proopiomelanocortin or leptin in the regulation of energy homeostasis.

Hypothalamic CART is a new anorectic peptide regulated by leptin

It is shown that CART (cocaine- and amphetamine-regulated transcript), a brain-located peptide, is a satiety factor and is closely associated with the actions of two important regulators of food intake, leptin and neuropeptide Y.

Tetrahydrocannabinol and endocannabinoids in feeding and appetite.