Leptin-regulated endocannabinoids are involved in maintaining food intake

Vincenzo Di Marzo, Sravan K. Goparaju, Lei Wang, Jie Liu, Sándor Bátkai, Z. Járai, Filomena Fezza, Grant I. Miura, Richard D. Palmiter, Takayuki Sugiura, George Kunos

Research output: Contribution to journalArticle

1232 Citations (Scopus)

Abstract

Leptin is the primary signal through which the hypothalamus senses nutritional state and modulates food intake and energy balance. Leptin reduces food intake by upregulating anorexigenic (appetite-reducing) neuropeptides, such as α-melanocyte-stimulating hormone, and downregulating orexigenic (appetite-stimulating) factors, primarily neuropeptide Y. Genetic defects in anorexigenic signalling, such as mutations in the melanocortin-4 (ref. 5) or leptin receptors, cause obesity. However, alternative orexigenic pathways maintain food intake in mice deficient in neuropeptide Y. CB1 cannabinoid receptors and the endocannabinoids anandamide and 2-arachidonoyl glycerol are present in the hypothalamus, and marijuana and anandamide stimulate food intake. Here we show 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. Furthermore, defective leptin signalling is associated with elevated hypothalarnic, but not cerebellar, levels of endocannabinoids in obese db/db and ob/ob mice and Zucker rats. Acute leptin treatment of normal rats and ob/ob mice reduces anandamide and 2-arachidonoyl glycerol in the hypothalamus. These findings indicate that endocannabinoids in the hypothalamus may tonically activate CB1 receptors to maintain food intake and form part of the neural circuitry regulated by leptin.

Original languageEnglish
Pages (from-to)822-825
Number of pages4
JournalNature
Volume410
Issue number6830
DOIs
Publication statusPublished - Apr 12 2001

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Endocannabinoids
Leptin
Eating
Cannabinoid Receptor CB1
Hypothalamus
rimonabant
Neuropeptide Y
Appetite
Knockout Mice
Melanocortins
Melanocyte-Stimulating Hormones
Zucker Rats
Leptin Receptors
Cannabis
Neuropeptides
Down-Regulation
Obesity
Food
Mutation
anandamide

ASJC Scopus subject areas

  • General

Cite this

Di Marzo, V., Goparaju, S. K., Wang, L., Liu, J., Bátkai, S., Járai, Z., ... Kunos, G. (2001). Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature, 410(6830), 822-825. https://doi.org/10.1038/35071088

Leptin-regulated endocannabinoids are involved in maintaining food intake. / Di Marzo, Vincenzo; Goparaju, Sravan K.; Wang, Lei; Liu, Jie; Bátkai, Sándor; Járai, Z.; Fezza, Filomena; Miura, Grant I.; Palmiter, Richard D.; Sugiura, Takayuki; Kunos, George.

In: Nature, Vol. 410, No. 6830, 12.04.2001, p. 822-825.

Research output: Contribution to journalArticle

Di Marzo, V, Goparaju, SK, Wang, L, Liu, J, Bátkai, S, Járai, Z, Fezza, F, Miura, GI, Palmiter, RD, Sugiura, T & Kunos, G 2001, 'Leptin-regulated endocannabinoids are involved in maintaining food intake', Nature, vol. 410, no. 6830, pp. 822-825. https://doi.org/10.1038/35071088
Di Marzo V, Goparaju SK, Wang L, Liu J, Bátkai S, Járai Z et al. Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature. 2001 Apr 12;410(6830):822-825. https://doi.org/10.1038/35071088
Di Marzo, Vincenzo ; Goparaju, Sravan K. ; Wang, Lei ; Liu, Jie ; Bátkai, Sándor ; Járai, Z. ; Fezza, Filomena ; Miura, Grant I. ; Palmiter, Richard D. ; Sugiura, Takayuki ; Kunos, George. / Leptin-regulated endocannabinoids are involved in maintaining food intake. In: Nature. 2001 ; Vol. 410, No. 6830. pp. 822-825.
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