Endocrine Abstracts

Obesity is characterized by an increase of endocannabinoid circulating levels as anandamide (AEA) and 2-arachidonoyl-glycerol (2AG). Whether these lipids represent a biomarker of dysmetabolism or merely reflect the fat mass spill-over is still unclear. After generating rigorous, gender specific, plasma reference intervals by 2D-liquid chromatography-tandem mass spectrometry, we defined the 97.5thcentile of endocannabinoid distribution in the normal population as the cut-off above which they are considered pathological: 2AG=4.23 and 3.12 pmol/ml; AEA=1.66 and 1.59 pmol/ml, in males (M) and females (F), respectively. By using the cut-off we analyzed the endocannabinoid levels in a 348M and 439F population (106 and 160 normal weight (NW), BMI≤24.9 kg/m²; 242 and 279 overweight/obese subjects, BMI≥25.0 kg/m²) aged 18–90 y. 3.8%M (n=4) and 9.4%F (n=15) of NW and 8.7%M (n=21) and 17.2%F (n=48) of overweight/obese showed elevated 2AG, while 3.8%M (n=4) and 9.4%F (n=15) of NW and 9.5%M (n=23) and 29.4%F (n=82) of overweight/obese displayed increased AEA, respectively, indicating that obese/overweight F have more frequently pathologically plasmatic AEA levels.

Within overweight/obese group, metabolic features were compared between subjects having normal or elevated 2AG and AEA levels. Males with elevated 2AG showed similar BMI but higher diastolic and systolic blood pressure (DBP and SBP, P=0.018 and P=0.006, respectively) and triglycerides (P=0.036) compared to those having 2AG in the normal range. Females with higher 2AG showed increased BMI (P=0.012), glycaemia (P=0.020) and triglycerides (P<0.0001), the latter maintaining the statistical significance after correction for BMI (P=0.0005). Both males and females with elevated AEA exhibited higher BMI and waist circumference compared to those with AEA in the normal range (P=0.025 and P<0.0001; P=0.014 and P=0.001, respectively). Females showing higher AEA had increased DBP, SBP and insulin even after correction for BMI (P=0.006, P=0.016 and P=0.032, respectively). In conclusion, circulating endocannabinoids are associated in a gender-specific fashion to cardiometabolic alterations independently from adiposity.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.