title: Differential alterations of the concentrations of endocannabinoids and related lipids in the subcutaneous adipose tissue of obese diabetic patients.
abstract: BACKGROUND
  The endocannabinoids, anandamide and 2-AG, are produced by adipocytes, where they stimulate lipogenesis via cannabinoid CB1 receptors and are under the negative control of leptin and insulin. Endocannabinoid levels are elevated in the blood of obese individuals and nonobese type 2 diabetes patients. To date, no study has evaluated endocannabinoid levels in subcutaneous adipose tissue (SAT) of subjects with both obesity and type 2 diabetes (OBT2D), characterised by similar adiposity and whole body insulin resistance and lower plasma leptin levels as compared to non-diabetic obese subjects (OB).
  
  
  METHODS
  The levels of anandamide and 2-AG, and of the anandamide-related PPARalpha ligands, oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), in the SAT obtained by abdominal needle biopsy in 10 OBT2D, 11 OB, and 8 non-diabetic normal-weight (NW) subjects, were measured by liquid chromatography-mass spectrometry. All subjects underwent a hyperinsulinaemic euglycaemic clamp.
  
  
  RESULTS
  As compared to NW, anandamide, OEA and PEA levels in the SAT were 2-4.4-fold elevated (p < 0.05), and 2-AG levels 2.3-fold reduced (p < .05), in OBT2D but not in OB subjects. Anandamide, OEA and PEA correlated positively (p < .05) with SAT leptin mRNA and free fatty acid during hyperinsulinaemic clamp, and negatively with SAT LPL activity and plasma HDL-cholesterol, which were all specifically altered in OBT2D subjects.
  
  
  CONCLUSIONS
  The observed alterations emphasize, for the first time in humans, the potential different role and regulation of adipose tissue anandamide (and its congeners) and 2-AG in obesity and type 2 diabetes.
authors.affiliation: Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Annuzzi
authors.forename: Fabiana
authors.initials: F
authors.lastname: Piscitelli
authors.forename: Lucrezia
authors.initials: L
authors.lastname: Di Marino
authors.forename: Lidia
authors.initials: L
authors.lastname: Patti
authors.forename: Rosalba
authors.initials: R
authors.lastname: Giacco
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Costabile
authors.forename: Lutgarda
authors.initials: L
authors.lastname: Bozzetto
authors.forename: Gabriele
authors.initials: G
authors.lastname: Riccardi
authors.forename: Roberta
authors.initials: R
authors.lastname: Verde
authors.forename: Stefania
authors.initials: S
authors.lastname: Petrosino
authors.forename: Angela A
authors.initials: AA
authors.lastname: Rivellese
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
mesh_terms: D050154:Adiposity; D000328:Adult; D000577:Amides; D001095:Arachidonic Acids / Q000378:metabolism; D063385:Cannabinoid Receptor Modulators / Q000032:analysis*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism*; D063388:Endocannabinoids; D004983:Ethanolamines; D005260:Female; D006801:Humans; D008055:Lipids / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D009829:Oleic Acids / Q000378:metabolism; D010169:Palmitic Acids / Q000378:metabolism; D053284:Polyunsaturated Alkamides / Q000378:metabolism; D050151:Subcutaneous Fat / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000577:Amides; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D004983:Ethanolamines; D008055:Lipids; D009829:Oleic Acids; D010169:Palmitic Acids; D053284:Polyunsaturated Alkamides; C488250:oleoylethanolamide; C005958:palmidrol; C078814:anandamide