Regulation of hypothalamic endocannabinoid levels by neuropeptides and hormones involved in food intake and metabolism: Insulin and melanocortins

Isabel Matias, Anna Valeria Vergoni, Stefania Petrosino, Alessandra Ottani, Alessandro Pocai, Alfio Bertolini, Vincenzo Di Marzo
Neuropharmacology. 2008-01-01; 54(1): 206-212
DOI: 10.1016/j.neuropharm.2007.06.011

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1. Neuropharmacology. 2008 Jan;54(1):206-12. doi:
10.1016/j.neuropharm.2007.06.011. Epub 2007 Jun 29.

Regulation of hypothalamic endocannabinoid levels by neuropeptides and hormones
involved in food intake and metabolism: insulin and melanocortins.

Matias I(1), Vergoni AV, Petrosino S, Ottani A, Pocai A, Bertolini A, Di Marzo

Author information:
(1)Endocannabinoid Research Group, Institute of Biomolecular Chemistry,
Consiglio Nazionale delle Ricerche, Via Campi Flegrei 34, 80078 Pozzuoli (NA),

Endocannabinoids are paracrine/autocrine lipid mediators with several biological
functions. One of these, i.e. the capability to stimulate food intake via
cannabinoid CB(1) receptors, has been particularly studied, thus leading to the
development of the first CB(1) receptor blocker, rimonabant, as a therapeutic
tool against obesity and related metabolic disorders. Hypothalamic
endocannabinoids stimulate appetite by regulating the expression and release of
anorexic and orexigenic neuropeptides via CB(1) receptors. In turn, the tone of
the latter receptors is regulated by hormones, including leptin, glucocorticoids
and possibly ghrelin and neuropeptide Y, by modulating the biosynthesis of the
endocannabinoids in various areas of the hypothalamus. CB(1) receptor
stimulation is also known to increase blood glucose during an oral glucose
tolerance test in rats. Here we investigated in the rat if insulin, which is
known to exert fundamental actions at the level of the mediobasal hypothalamus
(MBH), and the melanocortin system, namely alpha-melanocyte stimulating hormone
(alpha-MSH) and melanocortin receptor-4 (MCR-4), also regulate hypothalamic
endocannabinoid levels, measured by isotope-dilution liquid chromatography
coupled to mass spectrometry. No effect on anandamide and 2-arachidonoylglycerol
levels was observed after 2h infusion of insulin in the MBH, i.e. under
conditions in which the hormone reduces blood glucose, nor with
intra-cerebroventricular injection of alpha-MSH, under conditions in which the
neuropeptide reduces food intake. Conversely, blockade of MCR-4 receptors with
HS014 produced a late (6h after systemic administration) stimulatory effect on
endocannabinoid levels as opposed to a rapid and prolonged stimulation of
food-intake (observable 2 and 6h after administration). These data suggest that
inhibition of endocannabinoid levels does not mediate the effect of insulin on
hepatic glucose production nor the food intake-inhibitory effect of alpha-MSH,
although stimulation of endocannabinoid levels might underlie part of the late
stimulatory effects of MCR-4 blockade on food intake.

DOI: 10.1016/j.neuropharm.2007.06.011
PMID: 17675101 [Indexed for MEDLINE]

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