title: Endocannabinoid regulation in white and brown adipose tissue following thermogenic activation.
abstract: The endocannabinoids and their main receptor, cannabinoid type-1 (CB1), suppress intracellular cyclic AMP levels and have emerged as key players in the control of energy metabolism. CB1 agonists and blockers have been reported to influence the thermogenic function of white and brown adipose tissue (WAT and BAT), affecting body weight through the inhibition and stimulation of energy expenditure, respectively. The purpose of the current study was to investigate the regulation of the endocannabinoid system in WAT and BAT following exposure to either cold or specific agonism of β3-adrenoceptors using CL316,243 (CL), conditions known to cause BAT activation and WAT browning. To address this question, we performed quantitative PCR-based mRNA profiling of genes important for endocannabinoid synthesis, degradation, and signaling, and determined endocannabinoid levels by LC-MS in WAT and BAT of control, cold-exposed, and CL-treated wild-type mice as well as primary brown adipocytes. Treatment with CL and exposure to cold caused an upregulation of endocannabinoid levels and biosynthetic enzymes in WAT. Acute β3-adrenoceptor activation increased endocannabinoids and a subset of genes of biosynthesis in BAT and primary brown adipocytes. We suggest that the cold-mediated increase in endocannabinoid tone is part of autocrine negative feed-back mechanisms controlling β3-adrenoceptor-induced BAT activation and WAT browning.
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg Eppendorf, 20246 Hamburg, Germany.
authors.forename: Lucia M
authors.initials: LM
authors.lastname: Krott
authors.affiliation: Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, 80078 Pozzuoli, Naples, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Piscitelli
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg Eppendorf, 20246 Hamburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Heine
authors.affiliation: Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, 80078 Pozzuoli, Naples, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Borrino
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg Eppendorf, 20246 Hamburg, Germany.
authors.forename: Ludger
authors.initials: L
authors.lastname: Scheja
authors.affiliation: Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, 80078 Pozzuoli, Naples, Italy.
authors.forename: Cristoforo
authors.initials: C
authors.lastname: Silvestri
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg Eppendorf, 20246 Hamburg, Germany heeren@uke.uni-hamburg.de vdimarzo@icb.na.cnr.it.
authors.forename: Joerg
authors.initials: J
authors.lastname: Heeren
authors.affiliation: Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, 80078 Pozzuoli, Naples, Italy heeren@uke.uni-hamburg.de vdimarzo@icb.na.cnr.it.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
mesh_terms: D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D058667:Adrenergic beta-3 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D003080:Cold Temperature; D063388:Endocannabinoids / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism; D022722:Thermogenesis / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D058667:Adrenergic beta-3 Receptor Agonists; D063388:Endocannabinoids; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D022702:Receptors, Adrenergic, beta-3
keywords: cannabinoids; gene expression; phospholipids; protein kinases/protein kinase A