Astroglial CB1 cannabinoid receptors regulate leptin signaling in mouse brain astrocytes.
Molecular Metabolism. 2013-11-01; 2(4): 393-404
DOI: 10.1016/j.molmet.2013.08.001
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1. Mol Metab. 2013 Aug 9;2(4):393-404. doi: 10.1016/j.molmet.2013.08.001.
eCollection 2013.
Astroglial CB1 cannabinoid receptors regulate leptin signaling in mouse brain
astrocytes.
Bosier B(1), Bellocchio L, Metna-Laurent M, Soria-Gomez E, Matias I,
Hebert-Chatelain E, Cannich A, Maitre M, Leste-Lasserre T, Cardinal P,
Mendizabal-Zubiaga J, Canduela MJ, Reguero L, Hermans E, Grandes P, Cota D,
Marsicano G.
Author information:
(1)INSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale,
U862, F-33000 Bordeaux, France ; University of Bordeaux, Neurocentre Magendie,
Physiopathologie de la Plasticité Neuronale, U862, F-33000 Bordeaux, France ;
Neuropharmacology, Institute of Neurosciences, Université Catholique de Louvain,
Av. Hippocrate 54, B1.54.10-10, 1200 Bruxelles, Belgium.
Type-1 cannabinoid (CB1) and leptin (ObR) receptors regulate metabolic and
astroglial functions, but the potential links between the two systems in
astrocytes were not investigated so far. Genetic and pharmacological
manipulations of CB1 receptor expression and activity in cultured cortical and
hypothalamic astrocytes demonstrated that cannabinoid signaling controls the
levels of ObR expression. Lack of CB1 receptors also markedly impaired
leptin-mediated activation of signal transducers and activators of transcription
3 and 5 (STAT3 and STAT5) in astrocytes. In particular, CB1 deletion determined a
basal overactivation of STAT5, thereby leading to the downregulation of ObR
expression, and leptin failed to regulate STAT5-dependent glycogen storage in the
absence of CB1 receptors. These results show that CB1 receptors directly
interfere with leptin signaling and its ability to regulate glycogen storage,
thereby representing a novel mechanism linking endocannabinoid and leptin
signaling in the regulation of brain energy storage and neuronal functions.
DOI: 10.1016/j.molmet.2013.08.001
PMCID: PMC3854987
PMID: 24327955