Endocrine Abstracts (2017) 49 EP669 | DOI: 10.1530/endoabs.49.EP669

Menopause is a major determinant of endocannabinoid 2-arachidonoylglycerol plasma level and of its relevance as biomarker of dyslipidemia and insulin resistance in lean women

Flaminia Fanelli, Marco Mezzullo, Margherita Baccini, Elena Casadio, Daniela Ibarra Gasparini, Valentina Vicennati, Renato Pasquali & Uberto Pagotto


Endocrinology Unit and Center for Applied Biomedical Research Department of Clinical and Surgical Science, University of Bologna, S.Orsola-Malpighi Hospital, Bologna, Italy.


Context: The endocannabinoid system (ECS) hypertonicity contributes to obesity development and maintenance. Excess circulating levels of ECS mediator 2-arachidonoylglycerol (2AG) were reported in obese humans, however, unstandardized experimental settings (i.e. analytical conditions, sample size, concurrent diseases/medications, statistics, gender, body mass index (BMI) and age), clouded its role in dysmetabolism and its usefulness as biomarker. The study aimed at describing 2AG associations with visceral obesity, dyslipidaemia, insulin resistance and hypertension in females according to BMI and menopausal status.

Methods: Adult, unmedicated, disease-free premenopausal (preMP, n=103) and menopausal (MP, n=81) females were stratified in normal weight (NW, BMI:18.5–24.9kg/m2), overweight (OW; BMI: 25.0–29.9kg/m2) and obese (BMI ≥30.0kg/m2) classes. Plasma 2AG, anthropometric and metabolic parameters were assessed.

Results: Menopause (P<0.001) and BMI (P=0.001) independently increased 2AG levels. NW (P=0.001) and OW (P<0.001), but not OB, MP women, displayed higher 2AG than preMP counterparts. 2AG increased with BMI in preMP (P<0.001), but not in MP cohort. 2AG displayed BMI-independent relationships with triglycerides in both preMP (P=0.006) and MP (P=0.005) and with glucose in MP (P=0.036). When analyzed within preMP BMI classes, only in OB class 2AG significantly associated with total cholesterol (TC, P=0.040) and triglycerides (P=0.020). In MP cohort, 2AG associated with TC (P=0.006), glucose (P<0.001), HOMA-IR (P=0.035) and triglycerides (P=0.001) within NW, with triglycerides in OW (P=0.034) and with none of the parameters in OB class. Moreover, increasing BMI significantly reduced 2AG associations with TC (P=0.037) and glucose (P=0.002) in MP cohort, while 2AG associations with TC, glucose and HOMA-IR significantly distinguished NW MP from NW preMP women (P=0.036, P=0.005 and P=0.027, respectively). No 2AG associations were found with waist circumference and blood pressures.

Conclusions: Plasma 2AG is a valuable biomarker of clustering insulin resistance and dyslipidemia in lean menopausal women, and may play a causative role in menopause-related metabolic worsening.