title: Astroglial CB1 cannabinoid receptors regulate leptin signaling in mouse brain astrocytes.
abstract: 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.
authors: 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.
authors: Barbara
authors: B
authors: Bosier
authors: Luigi
authors: L
authors: Bellocchio
authors: Mathilde
authors: M
authors: Metna-Laurent
authors: Edgar
authors: E
authors: Soria-Gomez
authors: Isabelle
authors: I
authors: Matias
authors: Etienne
authors: E
authors: Hebert-Chatelain
authors: Astrid
authors: A
authors: Cannich
authors: Marlène
authors: M
authors: Maitre
authors: Thierry
authors: T
authors: Leste-Lasserre
authors: Pierre
authors: P
authors: Cardinal
authors: Juan
authors: J
authors: Mendizabal-Zubiaga
authors: Miren Josune
authors: MJ
authors: Canduela
authors: Leire
authors: L
authors: Reguero
authors: Emmanuel
authors: E
authors: Hermans
authors: Pedro
authors: P
authors: Grandes
authors: Daniela
authors: D
authors: Cota
authors: Giovanni
authors: G
authors: Marsicano
keywords: Astroglial CB1 receptors; Astroglial leptin receptor; CB1, type-1 cannabinoid receptor; Cannabinoid; Cx, cerebral cortex; FAAH, fatty acid amide hydrolase; GFAP, glial fibrillary acidic protein; Glycogen; Leptin signaling; MGL, monoacylglycerol lipase; ObR, leptin receptor; ObRb, long-isoform leptin receptor; P-STAT3, Tyr705-phosphorylated form of STAT3; P-STAT5, Tyr694-phosphorylated form of STAT5; STAT3 and 5; STAT3, transducers and activators of transcription 3; STAT5, transducers and activators of transcription 5; VMH, ventromedial hypothalamus