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

Abstract

Objective: 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 . Results: 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 (X30 kg/m 2 ) but who markedly differed in their amount of IAA (o vsX130 cm 2 , n ¼ 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. Conclusions: These results provide evidence for a relationship in men between a key endocannabinoid, 2-AG, and cardiometabolic risk factors, including IAA.

Changes in plasma endocannabinoid levels in viscerally obese men following a 1 year lifestyle modification programme and waist circumference reduction: associations with changes in metabolic risk factors

“…However, only the reduction in 2-AG correlated with intervention-induced beneficial changes in VAT, TG and HDL 3 -cholesterol, thus resembling in this way other metabolic factors such as leptin. Although with the unavoidable limitations of all correlative studies, the present results suggest a relationship between peripheral EC and CB 1 receptor activity (in as much as these can be measured by plasma 2-AG levels) and VAT and dyslipidaemia (high TG and low HDL-cholesterol levels), a relationship which is possibly stronger than that suggested by previous cross-sectional studies [3,4]. This finding is in agreement with the causative role, established in animal studies, of dysregulated EC levels in dyslipidaemia via direct actions on the adipose tissue and the liver [1].…”

“…Measurement of L4-L5 abdominal adipose tissue areas was performed by computed tomography [6]. Complete fasting plasma lipoprotein-lipid profile was obtained as described [4] and LDL particle size was measured by non-denaturing polyacrylamide gradient gel electrophoresis [7]. A 75 g OGTT was performed in the morning after an overnight fast.…”

“…A 75 g OGTT was performed in the morning after an overnight fast. Plasma glucose and insulin were measured as described [8,9] EC levels were measured by isotope-dilution liquid chromatography-atmospheric pressure chemical ionisation-mass spectrometry as described [4]. Fasting plasma adiponectin, leptin (B-Bridge International, Mountain View, CA, USA) and IL-6 (R&D Systems, Minneapolis, MN, USA) concentrations were determined by ELISA.…”

“…Therefore, it is not known if interventioninduced changes in EC levels correlate with changes in metabolic dysfunctions associated with VAT. Such an observation would establish a relationship between the overactive endocannabinoid system and some metabolic risk factors that is stronger than that implied by crosssectional studies [3,4]. In the present study, we aimed to obtain this information by investigating, in a sample of viscerally obese patients, the effect of a 1 year lifestyle modification programme, consisting of healthy eating and regular physical activity/exercise, on EC levels, VAT accumulation and metabolic cardiovascular risk factors.…”

“…In obese patients, higher levels of the EC, 2-arachidonoylglycerol (2-AG), but not of another EC, anandamide, are found in VAT, but not subcutaneous adipose tissue (SAT), as compared with lean volunteers [2]. In two independent cross-sectional studies, increased plasma levels of 2-AG, but not anandamide, were shown to correlate with high levels of VAT, but not SAT, as well as with several of the aforementioned metabolic alterations [3,4]. In view of the proposed pro-lipogenic and glucose intolerance-inducing actions of CB 1 receptor stimulation in rodents [1], an upregulated EC system in the VAT of obese patients might lead to an increased VAT accumulation and contribute to ectopic fat accumulation and insulin resistance.…”