Turku PET Centre, University of Turku, Turku, Finland.
Department of Endocrinology, Turku University Hospital, Turku, Finland.
Obesity (Silver Spring). 2023 Jul;31(7):1844-1858. doi: 10.1002/oby.23770.
Cannabinoid type 1 receptors (CB1R) modulate feeding behavior and energy homeostasis, and the CB1R tone is dysgulated in obesity. This study aimed to investigate CB1R availability in peripheral tissue and brain in young men with overweight versus lean men.
Healthy males with high (HR, n = 16) or low (LR, n = 20) obesity risk were studied with fluoride 18-labeled FMPEP-d positron emission tomography to quantify CB1R availability in abdominal adipose tissue, brown adipose tissue, muscle, and brain. Obesity risk was assessed by BMI, physical exercise habits, and familial obesity risk, including parental overweight, obesity, and type 2 diabetes. To assess insulin sensitivity, fluoro-[ F]-deoxy-2-D-glucose positron emission tomography during hyperinsulinemic-euglycemic clamp was performed. Serum endocannabinoids were analyzed.
CB1R availability in abdominal adipose tissue was lower in the HR than in the LR group, whereas no difference was found in other tissues. CB1R availability of abdominal adipose tissue and brain correlated positively with insulin sensitivity and negatively with unfavorable lipid profile, BMI, body adiposity, and inflammatory markers. Serum arachidonoyl glycerol concentration was associated with lower CB1R availability of the whole brain, unfavorable lipid profile, and higher serum inflammatory markers.
The results suggest endocannabinoid dysregulation already in the preobesity state.
大麻素 1 型受体 (CB1R) 调节摄食行为和能量平衡，肥胖时 CB1R 张力失调。本研究旨在研究超重和正常体重的年轻男性外周组织和大脑中的 CB1R 可用性。
研究人员使用氟-18 标记的 FMPEP-d 正电子发射断层扫描研究了具有高（HR，n=16）或低（LR，n=20）肥胖风险的健康男性，以量化腹部脂肪组织、棕色脂肪组织、肌肉和大脑中的 CB1R 可用性。肥胖风险通过 BMI、体育锻炼习惯以及包括父母超重、肥胖和 2 型糖尿病在内的家族肥胖风险来评估。为了评估胰岛素敏感性，在高胰岛素-正常血糖钳夹期间进行氟-[ F]-脱氧-2-D-葡萄糖正电子发射断层扫描。分析血清内源性大麻素。
与 LR 组相比，HR 组腹部脂肪组织中的 CB1R 可用性较低，而其他组织则没有差异。腹部脂肪组织和大脑的 CB1R 可用性与胰岛素敏感性呈正相关，与不良脂质谱、BMI、体脂肪和炎症标志物呈负相关。血清花生四烯酰甘油浓度与全脑 CB1R 可用性降低、不良脂质谱和更高的血清炎症标志物相关。
这些结果表明内源性大麻素在肥胖前期已经失调。
