Higher plasma levels of endocannabinoids and analogues are correlated with a worse cardiometabolic profile in middle-aged adults

Abstract

The increase in age-related comorbidities, such as cardiometabolic diseases, has become a global health priority. There is a growing need to find new parameters capable of improving the detection of cardiometabolic risk factors, and circulating endocannabinoids (eCBs) are a promising tool in this context. Here, we aimed to investigate the relationship between plasma levels of eCBs and their analogues with body composition and cardiometabolic risk factors in middleaged adults. Seventy-two individuals (54% women; 53.6 ± 5.1 years old) were included in this study. Plasma levels of eCBs and analogues were determined using liquid chromatography-tandem mass spectrometry. Body composition was measured by dual-energy X-ray absorptiometry. Cardiometabolic risk factors (i.e., glucose and lipid profile, blood pressure, liver and renal parameters, and gonadal hormones) were also assessed. The plasma levels of 1- and 2-arachidonylglycerol (1-AG&2-AG) were positively correlated with adiposity (all r ≥ 0.23, P < 0.05). Interestingly, the plasma levels of 1-AG&2-AG, arachidonoylethanolamide, and palmitoyl-ethanolamide were positively correlated with the homeostatic model assessment index – Insulin Resistance (HOMA-IR) (all r ≥ 0.32, P < 0.01). Our results also showed that high levels of 1-AG&2-AG, arachidonoylethanolamide, linoleoyl ethanolamide, and palmitoleoyl ethanolamide were correlated with poorer liver (all r ≥ 0.27, P < 0.05), kidney (all r ≥ 0.24, P < 0.05), and gonadal function parameters (testosterone: all r > 0.26, P < 0.05, SHBG: 1-AG&2-AG r=-0.33, P < 0.01). The plasma levels of some eCBs and analogues are correlated with a worse cardiometabolic profile in middle-aged adults.