目的:棕色脂肪组织(BAT)是肥胖的治疗靶点。18F-氟脱氧葡萄糖正电子发射断层扫描(18F-FDG-PET)通常用于量化人BAT质量和活性。BAT可检测的18F-FDG摄取与心脏代谢疾病患病率降低相关然而,18F-FDG摄取可能并不总是BAT产热的可靠标志,例如胰岛素抵抗可能降低葡萄糖摄取。解偶联蛋白1(UCP1)是BAT中的关键产热蛋白。因此,我们假设UCP1表达在有心脏代谢危险因素的个体中可能发生改变.
方法:我们定量了UCP1表达作为BAT和白色脂肪组织(WAT)样品(n=53)以及分化的棕色和白色前脂肪细胞(n=85)的产热能力的替代标记。
结果:UCP1在BAT中的表达,但不在WAT或棕色/白色分化的前脂肪细胞中,随着年龄的增长而减少,肥胖和心血管代谢不良危险因素,如空腹血糖,胰岛素和血压。然而,在40岁的肥胖受试者中,BAT中的UCP1表达得以保留。为了确定BAT活性是否也在体内保存,我们进行了病例对照研究,在年轻(平均年龄~22y)正常体重和肥胖志愿者轻度冷暴露期间进行18F-FDG扫描。BAT摄取18F-FDG和BAT体积在组间相似,尽管胰岛素抵抗增加。
结论:在年轻的肥胖成人中,BAT对18F-FDG的摄取和UCP1的表达得以保留。年龄较大的受试者保留具有形成新的生热脂肪细胞的能力的前体细胞。这些数据突出了在肥胖中BAT质量扩张和活化的治疗潜力。
OBJECTIVE: Brown adipose tissue (BAT) is a therapeutic target for obesity. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) is commonly used to quantify human BAT mass and activity. Detectable 18F-FDG uptake by BAT is associated with reduced prevalence of cardiometabolic disease. However, 18F-FDG uptake may not always be a reliable marker of BAT thermogenesis, for example, insulin resistance may reduce glucose uptake. Uncoupling protein 1 (
UCP1) is the key thermogenic protein in BAT. Therefore, we hypothesised that
UCP1 expression may be altered in individuals with cardiometabolic risk factors.
METHODS: We quantified
UCP1 expression as an alternative marker of thermogenic capacity in BAT and white adipose tissue (WAT) samples (n = 53) and in differentiated brown and white pre-adipocytes (n = 85).
RESULTS: UCP1 expression in BAT, but not in WAT or brown/white differentiated pre-adipocytes, was reduced with increasing age, obesity, and adverse cardiometabolic risk factors such as fasting glucose, insulin, and blood pressure. However,
UCP1 expression in BAT was preserved in obese subjects of <40 years of age. To determine if BAT activity was also preserved in vivo, we undertook a case-control study, performing 18F-FDG scanning during mild cold exposure in young (mean age ∼22 years) normal weight and obese volunteers. 18F-FDG uptake by BAT and BAT volume were similar between groups, despite increased insulin resistance.
CONCLUSIONS: 18F-FDG uptake by BAT and UCP1 expression are preserved in young obese adults. Older subjects retain precursor cells with the capacity to form new thermogenic adipocytes. These data highlight the therapeutic potential of BAT mass expansion and activation in obesity.