Circulating endocannabinoid levels, abdominal adiposity and related cardiometabolic risk factors in obese men

The link between excess intra-abdominal adiposity (IAA) and metabolic complications leading to type 2 diabetes and cardiovascular disease is well recognized. Blockade of endocannabinoid action at cannabinoid CB(1) receptors was shown to reduce these complications. Here, we investigated the relationship between IAA, circulating endocannabinoid levels and markers of cardiometabolic risk in male obese subjects. DESIGN, SUBJECTS AND MEASUREMENTS: Fasting plasma levels of the endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), were measured by liquid chromatography-mass spectrometry in a study sample of 62 untreated asymptomatic men with body mass index (BMI) from 18.7 to 35.2 kg/m(2). Plasma 2-AG, but not AEA, levels correlated positively with BMI, waist girth, IAA measured by computed tomography, and fasting plasma triglyceride and insulin levels, and negatively with high-density lipoprotein cholesterol and adiponectin levels. Obese men with similar BMI values (> or =30 kg/m(2)) but who markedly differed in their amount of IAA (< vs > or = 130 cm(2), n=17) exhibited higher 2-AG levels in the presence of high IAA. No difference in 2-AG concentrations was observed between obese men with low levels of IAA vs nonobese controls. These results provide evidence for a relationship in men between a key endocannabinoid, 2-AG, and cardiometabolic risk factors, including IAA.