Endocrine Abstracts

Context: Ageing and obesity are similarly characterized by metabolic impairment in terms of visceral fat, dyslipidaemia, insulin resistance and hypertension. Obesity is featured by endocannabinoid system (ECS) hyperactivation. Increased levels of endocannabinoid 2-arachidonoylglycerol (2AG) found in obesity were variously associated to dysmetabolic features, however, it is not clear whether such associations exist in normal weight conditions. Moreover, ageing contribute in modulating 2AG tone and involvement in worsening metabolic profiles was not addressed. The study aimed at defining 2AG relevance as BMI-independent biomarker of metabolic impairment in males and whether its relevance is modified by ageing.

Methods: Unmedicated, disease-free male volunteers (n=144) aged 18-84yo were stratified in normal weight (NW, BMI:18.5–24.9 kg/m², n=61), overweight (OW; BMI: 25.0–29.9 kg/m², n=61) and obese (BMI ≥30.0 kg/m², n=22) classes. Plasma 2AG, anthropometric and metabolic parameters were assessed.

Results: Age did not influence 2AG levels in the overall cohort nor within BMI classes. 2AG levels increased with BMI (P=0.019), however, significance was lost after adjustment for each metabolic parameter. 2AG displayed age- and BMI-independent positive relationships with SBP (P=0.020), insulin (P=0.011), HOMA-IR (P=0.006), total cholesterol (P=0.001) and triglycerides (P<0.001) and negative with HDL-cholesterol (P=0.046). 2AG correlation with triglycerides was confirmed in each BMI class (NW and OW: P<0.001; OB: P=0.029). Positive 2AG correlation was found with SBP (P=0.023) and DBP (P=0.048) within OB, and with total cholesterol within OW (P<0.001) class. Finally, within the NW class, 2AG negatively associated with HDL-cholesterol (P=0.004) and positively with glucose (P=0.015), insulin (P=0.003) and HOMA-IR (P=0.001); notably, the last two correlations were positively influenced by age (both P=0.004). No associations were detected between 2AG and waist circumference.

Conclusions: Plasma 2AG is a valuable biomarker of clustering hypertension, insulin resistance and dyslipidemia in male gender. Results in lean males may suggest a causative role for 2AG in age-related insulin resistance.