Dion Dany, Noll Christophe, Fortin Mélanie, Haroune Lounès, Saibi Sabrina, Sarret Philippe, Carpentier André C
Division of Endocrinology, Department of Medicine, Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.
Department of Pharmacology & Pharmacology, Institut de Pharmacologie de Sherbrooke, Bioanalysis Platform, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.
J Clin Endocrinol Metab. 2025 May 19;110(6):e1821-e1832. doi: 10.1210/clinem/dgae657.
Little is known about the link between the endocannabinoid (EC) system and the in vivo metabolic function of white adipose tissue (WAT).
We aimed to evaluate whether ECs are linked to postprandial fatty acid metabolism and WAT metabolic function.
Men and women, with (IGT, n = 20) or without impaired glucose tolerance (NGT, n = 20) underwent meal testing with oral and intravenous stable isotope palmitate tracers and positron emission tomography with intravenous [11C]-palmitate and oral [18F]-fluoro-thia-heptadecanoic acid to determine systemic and organ-specific dietary fatty acid (DFA) and nonesterified fatty acid (NEFA) metabolism and partitioning. We determined fasting and postprandial plasma levels of EC by ultra-high performance liquid chromatography-tandem mass spectrometry.
All ECs of the 2-monoacylglycerol (2-MAG) family displayed a progressive postprandial increase up to 360 minutes after meal intake that was more pronounced in women with IGT. N-acylethanolamine (NAE) levels decreased between fasting and 180 minutes, followed by a return to preprandial values at 360 minutes and were also increased in women with IGT. Postprandial area under the curve (AUC) of palmitate appearance rate was significantly and independently associated with postprandial AUC of anandamide (AEA; P = .0003) and total energy expenditure (P = .0009). DFA storage in abdominal subcutaneous adipose tissue was positively predicted by fasting 2-arachidonoylglycerol (2-AG; P < .04).
EC levels of the NAE family independently follow plasma NEFA metabolism, whereas 2-MAG closely follow the spillover of triglyceride-rich lipoprotein intravascular lipolytic products. Whether these associations are causal requires further investigation.
关于内源性大麻素（EC）系统与白色脂肪组织（WAT）的体内代谢功能之间的联系，人们了解甚少。
我们旨在评估内源性大麻素是否与餐后脂肪酸代谢和白色脂肪组织代谢功能相关。
有（糖耐量受损，IGT，n = 20）或无糖耐量受损（正常糖耐量，NGT，n = 20）的男性和女性接受了口服和静脉注射稳定同位素棕榈酸示踪剂的餐食测试，以及静脉注射[11C]-棕榈酸和口服[18F]-氟硫十七烷酸的正电子发射断层扫描，以确定全身和器官特异性膳食脂肪酸（DFA）和非酯化脂肪酸（NEFA）的代谢及分配情况。我们通过超高效液相色谱-串联质谱法测定空腹和餐后血浆内源性大麻素水平。
2-单酰甘油（2-MAG）家族的所有内源性大麻素在餐后360分钟内均呈现出逐渐升高的趋势，在患有IGT的女性中更为明显。N-酰基乙醇胺（NAE）水平在空腹至180分钟之间下降，随后在360分钟时恢复到餐前值，且在患有IGT的女性中也有所升高棕榈酸出现率的餐后曲线下面积（AUC）与花生四烯乙醇胺（AEA）的餐后AUC（P = 0.0003）和总能量消耗（P = 0.0009）显著且独立相关。空腹2-花生四烯酸甘油酯（2-AG）可正向预测腹部皮下脂肪组织中的膳食脂肪酸储存（P < 0.04）。
NAE家族的内源性大麻素水平独立地随血浆非酯化脂肪酸代谢而变化，而2-MAG则紧密跟随富含甘油三酯的脂蛋白血管内脂解产物的溢出情况。这些关联是否具有因果关系需要进一步研究。
