title: Human adipose tissue binds and metabolizes the endocannabinoids anandamide and 2-arachidonoylglycerol.
abstract: Endocannabinoids are a group of biologically active endogenous lipids that have recently emerged as important mediators in energy balance control. The two best studied endocannabinoids, anandamide (N-arachidonoylethanolamine, AEA) and 2-arachidonoylglycerol (2-AG) are the endogenous ligands of the central and peripheral cannabinoid receptors. Furthermore, AEA binds to the transient receptor potential vanilloid type-1 (TRPV1), a capsaicin-sensitive, non-selective cation channel. The synthesis of these endocannabinoids is catalyzed by the N-acylphosphatidylethanolamine-selective phospholipase D (NAPE-PLD) and the sn-1-selective diacylglycerol lipase (DAGL), whereas their degradation is accomplished by the fatty acid amide hydrolase (FAAH) and the monoglyceride lipase (MGL), respectively. We investigated the presence of a functional endocannabinoid system in human adipose tissue from seven healthy subjects. Subcutaneous abdominal adipose tissue underwent biochemical and molecular biology analyses, aimed at testing the expression of this system and its functional activity. AEA and 2-AG levels were detected and quantified by HPLC. Real time PCR analyzed the expression of the endocannabinoid system and immunofluorescence assays showed the distribution of its components in the adipose tissue. Furthermore, binding assay for the cannabinoid and vanilloid receptors and activity assay for each metabolic enzyme of the endocannabinoid system gave clear evidence of a fully operating system. The data presented herein show for the first time that the human adipose tissue is able to bind AEA and 2-AG and that it is endowed with the biochemical machinery to metabolize endocannabinoids.
authors.affiliation: CNR-IBIM, National Research Council Institute of Biomedicine-Clinical Epidemiology and Physiophatology of Renal Disease and Hypertension & Urology Unit, c/o Ki Point-Gransial Srl, Via Filippini, n.85, 89125 Reggio Calabria, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Spoto
authors.forename: F
authors.initials: F
authors.lastname: Fezza
authors.forename: G
authors.initials: G
authors.lastname: Parlongo
authors.forename: N
authors.initials: N
authors.lastname: Battista
authors.forename: E
authors.initials: E
authors.lastname: Sgro'
authors.forename: V
authors.initials: V
authors.lastname: Gasperi
authors.forename: C
authors.initials: C
authors.lastname: Zoccali
authors.forename: M
authors.initials: M
authors.lastname: Maccarrone
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D001095:Arachidonic Acids / Q000378:metabolism*; D001483:Base Sequence; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D063388:Endocannabinoids; D005260:Female; D005455:Fluorescent Antibody Technique; D005989:Glycerides / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D053284:Polyunsaturated Alkamides / Q000378:metabolism*; D012313:RNA / Q000235:genetics / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism
chemical_list: D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005989:Glycerides; D053284:Polyunsaturated Alkamides; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D050916:TRPV Cation Channels; D012313:RNA; C094503:glyceryl 2-arachidonate; C078814:anandamide