Endocrinology Unit and Center for Applied Biomedical Research, Department of Medical and Surgical Sciences, Alma Mater University of Bologna, S. Orsola-Malpighi Hospital, via Massarenti 9, 40138, Bologna, Italy.
Department of Medical and Surgical Sciences, Alma Mater University of Bologna, S. Orsola-Malpighi Hospital, via Massarenti 9, 40138, Bologna, Italy.
Mol Metab. 2017 Mar 21;6(5):406-415. doi: 10.1016/j.molmet.2017.03.005. eCollection 2017 May.
The endocannabinoid system hypertonicity features obesity. Excess circulating 2-arachidonoylglycerol was variously associated with obesity-related metabolic impairment; however, unstandardized experimental and analytical settings have clouded its usefulness as a dysmetabolism biomarker. We aimed at assessing the influence of body mass index (BMI), menopause in women, and aging in men on 2-arachidonoylglycerol relationship with metabolic parameters.
Adult, unmedicated women (premenopausal (preMW): n = 103; menopausal (MW): n = 81) and men (n = 144) were stratified in normal weight (NW; BMI: 18.5-24.9 kg/m), overweight (OW; BMI: 25.0-29.9 kg/m), and obese (OB; BMI ≥ 30.0 kg/m) classes. Anthropometric and metabolic parameters were determined. Plasma 2-arachidonoylglycerol was measured by a validated liquid chromatography-mass spectrometry assay.
2-arachidonoylglycerol level was raised by menopause (P < 0.001) and by obesity in preMW (P < 0.001) and in men (P = 0.019). In the overall cohorts, 2-arachidonoylglycerol displayed BMI-independent relationships with dyslipidemia (preMW, MW and men), insulin resistance (MW and men), and hypertension (men), but not with waist circumference. Within preMW BMI classes, 2-arachidonoylglycerol correlations were found with triglycerides (P = 0.020) and total cholesterol (TC; P = 0.040) in OB women. In MW, 2-arachidonoylglycerol correlation with triglycerides was found in NW (P = 0.001) and OW (P = 0.034), but not in OB class. Moreover, we found 2-arachidonoylglycerol correlations with TC (P = 0.003), glucose (P < 0.001), and HOMA-IR (P = 0.035) specific for NW MW class. In men, 2-arachidonoylglycerol correlated with triglycerides in NW, OW (both P < 0.001), and OB (P = 0.029), with SBP (P = 0.023) and diastolic BP (DBP; P = 0.048) in OB, and with TC (P < 0.001) in OW class. In NW class 2-arachidonoylglycerol correlations were found with insulin (P = 0.003) and HOMA-IR (P = 0.001), both enhanced by aging (both P = 0.004), and with glucose (P = 0.015) and HDL (P = 0.004).
Plasma 2AG is a biomarker of clustering metabolic dysfunctions, especially in lean men and menopausal women, and could be of help in identifying subjects with elevated cardiometabolic risk despite a healthy anthropometric appearance.
内源性大麻素系统张力特征为肥胖。循环中过量的 2-花生四烯酸甘油与肥胖相关代谢损伤有关;然而,实验和分析设置的不规范使它作为代谢紊乱生物标志物的作用变得模糊。我们旨在评估体重指数(BMI)、女性绝经和男性衰老对 2-花生四烯酸甘油与代谢参数关系的影响。
将成年、未服用药物的女性(绝经前(preMW):n=103;绝经后(MW):n=81)和男性(n=144)分为正常体重(NW;BMI:18.5-24.9 kg/m)、超重(OW;BMI:25.0-29.9 kg/m)和肥胖(OB;BMI≥30.0 kg/m)组。测定人体测量和代谢参数。用经验证的液相色谱-质谱法测定血浆 2-花生四烯酸甘油。
绝经(P<0.001)和肥胖(preMW 和男性中的 P<0.001)增加了 2-花生四烯酸甘油水平。在整个队列中,2-花生四烯酸甘油与血脂异常(preMW、MW 和男性)、胰岛素抵抗(MW 和男性)和高血压(男性)呈 BMI 独立相关,但与腰围无关。在 preMW BMI 类别中,2-花生四烯酸甘油与女性 OB 组的甘油三酯(P=0.020)和总胆固醇(TC;P=0.040)呈相关性。在 MW 中,在 NW(P=0.001)和 OW(P=0.034)中发现 2-花生四烯酸甘油与甘油三酯的相关性,但在 OB 类中没有发现。此外,我们发现 2-花生四烯酸甘油与 TC(P=0.003)、葡萄糖(P<0.001)和 HOMA-IR(P=0.035)呈特定的相关性,仅在 NW MW 类中发现。在男性中,2-花生四烯酸甘油与 NW、OW(均 P<0.001)和 OB(P=0.029)中的甘油三酯、OB 中的 SBP(P=0.023)和 DBP(P=0.048)以及 OW 类中的 TC(P<0.001)呈相关性。在 NW 类中,发现 2-花生四烯酸甘油与胰岛素(P=0.003)和 HOMA-IR(P=0.001)呈相关性,这两者均随年龄增长而增强(均 P=0.004),并且与葡萄糖(P=0.015)和 HDL(P=0.004)呈相关性。
血浆 2-花生四烯酸甘油是代谢功能障碍聚集的生物标志物,特别是在瘦男性和绝经后女性中,并且可能有助于识别尽管具有健康的人体测量外观但心血管代谢风险升高的个体。