Plasma 2-arachidonoylglycerol is a biomarker of age and menopause related insulin resistance and dyslipidemia in lean but not in obese men and women

• Published in: Molecular metabolism (Germany) Vol. 6; no. 5; pp. 406 - 415
• Main Authors: Fanelli, Flaminia, Mezzullo, Marco, Belluomo, Ilaria, Di Lallo, Valentina Diana, Baccini, Margherita, Ibarra Gasparini, Daniela, Casadio, Elena, Mastroroberto, Marianna, Vicennati, Valentina, Gambineri, Alessandra, Morselli-Labate, Antonio Maria, Pasquali, Renato, Pagotto, Uberto
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 01.05.2017; Elsevier
• Subjects: 2-Arachidonoylglycerol; Aging; Dysmetabolism; Endocannabinoid system; Endocrinology & Metabolism; Menopause; Obesity; Original; SBP; Obesity; Menopause; OW; 2-Arachidonoylglycerol; NW; Int; HDL; HOMA-IR; LC-MS/MS; SD; Endocannabinoid system; Dysmetabolism; DBP; OB; ECS; 1AG; Aging; 2AG; EC; BMI; endocannabinoid; 1-arachidonoylglycerol; systolic blood pressure; obese; diastolic blood pressure; overweight; homeostatic model assessment of insulin resistance; normal weight; body mass index; 2-arachidonoylglycerol; interaction; liquid chromatography-tandem mass spectrometry; high density lipoprotein; standard deviation; OW, overweight; 1AG, 1-arachidonoylglycerol; ECS, endocannabinoid system; LC-MS/MS, liquid chromatography-tandem mass spectrometry; DBP, diastolic blood pressure; HDL, high density lipoprotein; Int, interaction; NW, normal weight; SBP, systolic blood pressure; BMI, body mass index; SD, standard deviation; 2AG, 2-arachidonoylglycerol; EC, endocannabinoid; HOMA-IR, homeostatic model assessment of insulin resistance; OB, obese
• ISSN: 2212-8778; 2212-8778
• DOI: 10.1016/j.molmet.2017.03.005

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/m2), overweight (OW; BMI: 25.0–29.9 kg/m2), and obese (OB; BMI ≥ 30.0 kg/m2) 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. •Plasma 2AG is a biomarker of dysmetabolism rather than obesity.•Menopause is a major determinant of plasma 2AG levels in females.•Increased plasma 2AG level features obese premenopausal females and obese males.•2AG is a biomarker of dyslipidemia and insulin resistance in lean menopausal women.•2AG is a biomarker of dyslipidemia and age-related insulin resistance in lean men. [Display omitted]