Differential alterations of the concentrations of endocannabinoids and related lipids in the subcutaneous adipose tissue of obese diabetic patients.
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.
Annuzzi
Giovanni
G
Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy.
Piscitelli
Fabiana
F
Di Marino
Lucrezia
L
Patti
Lidia
L
Giacco
Rosalba
R
Costabile
Giuseppina
G
Bozzetto
Lutgarda
L
Riccardi
Gabriele
G
Verde
Roberta
R
Petrosino
Stefania
S
Rivellese
Angela A
AA
Di Marzo
Vincenzo
V
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
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