| First Author | Cardinal P | Year | 2012 |
| Journal | Endocrinology | Volume | 153 |
| Issue | 9 | Pages | 4136-43 |
| PubMed ID | 22778221 | Mgi Jnum | J:189170 |
| Mgi Id | MGI:5444568 | Doi | 10.1210/en.2012-1405 |
| Citation | Cardinal P, et al. (2012) Hypothalamic CB1 cannabinoid receptors regulate energy balance in mice. Endocrinology 153(9):4136-43 |
| abstractText | Cannabinoid type 1 (CB(1)) receptor activation is generally considered a powerful orexigenic signal and inhibition of the endocannabinoid system is beneficial for the treatment of obesity and related metabolic diseases. The hypothalamus plays a critical role in regulating energy balance by modulating both food intake and energy expenditure. Although CB(1) receptor signaling has been implicated in the modulation of both these mechanisms, a complete understanding of its role in the hypothalamus is still lacking. Here we combined a genetic approach with the use of adeno-associated viral vectors to delete the CB(1) receptor gene in the adult mouse hypothalamus and assessed the impact of such manipulation on the regulation of energy balance. Viral-mediated deletion of the CB(1) receptor gene in the hypothalamus led to the generation of Hyp-CB(1)-KO mice, which displayed an approximately 60% decrease in hypothalamic CB(1) receptor mRNA levels. Hyp-CB(1)-KO mice maintained on a normocaloric, standard diet showed decreased body weight gain over time, which was associated with increased energy expenditure and elevated beta(3)-adrenergic receptor and uncoupling protein-1 mRNA levels in the brown adipose tissue but, surprisingly, not to changes in food intake. Additionally, Hyp-CB(1)-KO mice were insensitive to the anorectic action of the hormone leptin (5 mg/kg) and displayed a time-dependent hypophagic response to the CB(1) inverse agonist rimonabant (3 mg/kg). Altogether these 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. |
