title: Cannabinoid CB1 receptor expression in relation to visceral adipose depots, endocannabinoid levels, microvascular damage, and the presence of the Cnr1 A3813G variant in humans.
abstract: Dysregulation of the endocannabinoid system in the visceral adipose tissue (VAT) is associated with metabolic and cardiovascular complications of obesity. We studied perirenal VAT CB1 receptor expression in relation to anthropometry, VAT area and endocannabinoid levels, kidney microvascular damage (MVDa), and the presence of the CB1 gene A3813G variant, the frequency of which was also evaluated in a large population of obese-hypertensive (OH) patients with or without the metabolic syndrome (MetS). Perirenal VAT and kidney samples were obtained from 30 patients undergoing renal surgery. Total and perirenal VAT areas were determined by computed tomography. CB1 messenger RNA expression and endocannabinoid levels in perirenal VAT were determined by quantitative reverse transcriptase polymerase chain reaction and liquid chromatography-mass spectrometry, respectively. The MVDa was evaluated in healthy portions of kidney cortex. The A3813G alleles were identified by genotyping in these patients and in 280 nondiabetic OH patients (age <or=65 years). Metabolic syndrome was defined according to the Adult Treatment Panel III criteria. Perirenal VAT CB1 expression was 40% lower in patients with the A3813G polymorphism, and correlated positively with perirenal and total VAT area and with perirenal VAT levels of the endocannabinoid anandamide. A 2-fold higher CB1 expression was associated with MVDa. The OH patients with the A3813G allele had lower prevalence of MetS in both unadjusted and adjusted models. Genetics influence perirenal VAT CB1 expression and the prevalence of MetS in OH. Increased VAT is associated with increased perirenal VAT endocannabinoid tone, which in turn correlates with increased MVDa. Endocannabinoid overactivity might be involved in human visceral obesity and its renal complications.
authors.affiliation: Department of Internal Medicine, University of Ancona-Politecnica delle Marche, University Hospital of Ancona, Ancona, Italy.
authors.forename: Marica
authors.initials: M
authors.lastname: Bordicchia
authors.forename: Ilaria
authors.initials: I
authors.lastname: Battistoni
authors.forename: Lucia
authors.initials: L
authors.lastname: Mancinelli
authors.forename: Elena
authors.initials: E
authors.lastname: Giannini
authors.forename: Giada
authors.initials: G
authors.lastname: Refi
authors.forename: Daniele
authors.initials: D
authors.lastname: Minardi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Muzzonigro
authors.forename: Roberta
authors.initials: R
authors.lastname: Mazzucchelli
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Montironi
authors.forename: Fabiana
authors.initials: F
authors.lastname: Piscitelli
authors.forename: Stefania
authors.initials: S
authors.lastname: Petrosino
authors.forename: Paolo
authors.initials: P
authors.lastname: Dessì-Fulgheri
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rappelli
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
authors.forename: Riccardo
authors.initials: R
authors.lastname: Sarzani
mesh_terms: D052242:Adiponectin / Q000097:blood; D000368:Aged; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D063388:Endocannabinoids; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D050152:Intra-Abdominal Fat / Q000378:metabolism* / Q000473:pathology; D016015:Logistic Models; D008297:Male; D055806:Microvessels; D008875:Middle Aged; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D043884:Receptor, Cannabinoid, CB1 / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014057:Tomography, X-Ray Computed
chemical_list: D052242:Adiponectin; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1