Appetite Mice with the Munchies

Leptin is a hypothalamic hormone that supresses food intake; cannabis is a well-known appetite stimulant (see Mechoulam and Fride). Di Marzo et al. show that leptin regulates the levels of endogenous cannabinoids, although the mechanism underlying this regulation remains ambiguous. Genetic deletion of the cannabinoid receptor CB1 decreases food intake, and this decrease in appetite can be reproduced in wild-type mice by antagonism of the CB1 receptor. Leptin injection decreases endogenous cannabinoid levels in the hypothalamus. Obese mice with defective leptin signaling [fa/fa Zucker mice, db/db mice (defective leptin receptor), and ob/ob mice (leptin deficient)] exhibit enhanced levels of endogenous cannabinoids, suggesting that uncontrolled cannabinoids' signaling may be contributing to the increased food intake in these animals. In ob/ob mice and db/db mice, treatment with the CB1 antagonist suppressed eating. In neuropeptide Y-deficient animals, treatment with the CB1 antagonist decreased food intake, suggesting that cannabinoids and neuropeptide Y may redundantly and independently regulate appetite.

R. Mechoulam, E. Fride, Physiology: A hunger for cannabinoids. Nature 410, 763-765 (2001). [Online Journal]

V. Di Marzo, S. K. Goparaju, L. Wang, J. Liu, S. Bátkai, Z. Járai, F. Fezza, G. I. Miura, R. D. Palmiter, T. Sugiura, G. Kunos, Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature 410, 822-825 (2001). [Online Journal]