Differential alterations of the concentrations of endocannabinoids and related lipids in the subcutaneous adipose tissue of obese diabetic patients

Giovanni Annuzzi,Giuseppina Costabile,Vincenzo Di Marzo,Angela A Rivellese,Lidia Patti,Rosalba Giacco,Lutgarda Bozzetto,Roberta Verde,Gabriele Riccardi,Lucrezia Di Marino,Fabiana Piscitelli,Stefania Petrosino

doi:10.1186/1476-511x-9-43

Giovanni Annuzzi, Giuseppina Costabile + Show 10 more

Open Access

https://doi.org/10.1186/1476-511x-9-43

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Abstract

BackgroundThe 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).Design and MethodsThe levels of anandamide and 2-AG, and of the anandamide-related PPARα 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.ResultsAs 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.ConclusionsThe 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.

Highlights

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
Anandamide, OEA and PEA correlated positively (p < .05) with subcutaneous adipose tissue (SAT) leptin mRNA and free fatty acid during hyperinsulinaemic clamp, and negatively with SAT LPL activity and plasma HDL-cholesterol, which were all altered in obesity and type 2 diabetes (OBT2D) subjects
No such studies have been performed to date in the white adipose tissue (WAT) of obese patients with type 2 diabetes, who can be characterised by similar whole body insulin resistance, but lower plasma leptin levels, as compared to matched non diabetic obese subjects [18,19]

Summary

Introduction

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. 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). As opposed to obese rodents [13], reduced levels of FAAH expression have been reported for obese subjects in the subcutaneous adipose tissue (SAT) [9,16,17], where, instead, there seems to be no elevation of endocannabinoid levels [3] No such studies have been performed to date in the WAT of obese patients with type 2 diabetes, who can be characterised by similar whole body insulin resistance, but lower plasma leptin levels, as compared to matched non diabetic obese subjects [18,19]

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