OR07-03 UCP1 Expression In Human Brown Adipose Tissue Is Inversely Associated With Cardiometabolic Risk Factors
OR07-03 UCP1 Expression In Human Brown Adipose Tissue Is Inversely Associated With Cardiometabolic Risk Factors
复制标题
人棕色脂肪组织中OR07-03 UCP1的表达与心脏代谢危险因素负相关
DOI：
10.1210/jendso/bvad114.005
复制
发表时间：
2023-10-05
影响因子：
4.1
通讯作者：
Stimson RH
中科院分区：
文献类型：
--
作者：
Kwok TC;Ramage LE;Suchacki KJ;Gray C;Alexandra K;Boyle LD;Semple RK;Semple SI;MacGillivray T;van Beek EJ;Wakelin S;Stimson RH
披露：郭炳江：没有。L.E.拉马奇：没有。K.J.Suchacki：没有。C.格雷：没有。亚力山德拉：没有。L.D.博伊尔：没有。RK.Sample：没有。S.I.Sample：没有。T·麦吉利夫雷：没有。E.J.范·毕克：没有。韦克林：没有。R.H.史汀生：没有。棕色脂肪组织(BAT)是一种很有前途的肥胖症治疗靶点。18F-脱氧葡萄糖正电子发射断层扫描(18F-FDGPET)是最常用的定量人体BAT活动的成像方法。肥胖患者对18F-FDG的摄取可能减少，但胰岛素抵抗被认为是一个潜在的混杂因素。解偶联蛋白1(UCP1)是蝙蝠体内关键的生热蛋白，可作为BAT生热能力的替代指标。我们对141例接受择期颈部手术的患者的BAT和白色脂肪组织(WAT)样本中UCP1的表达进行了量化。UCP1在整个组织(n=53)和分化前脂肪细胞(n=88)中均有定量表达。数据采用均值±扫描电镜(Mean±SEM)表示。在整个蝙蝠中UCP1高表达的个体(>；体重指数(26.5±1.2vs30.1±1.0 kg/m2)、腰围(87.9±2.9vs101.1±2.6 cm)、腰臀比(0.86±0.01vs0.92±0.01)、脂肪百分比(29.1±2.6vs35.3±1.7%)，胰岛素抵抗(HOMA-IR 1.44±0.18 vs 2.69±0.35)、收缩压(131±6 vs 143±4 mm Hg)、舒张压(79±3 vs 86±2 mm Hg)(P均<0.01)；0.05)。服用β-受体阻滞剂或有高血压的受试者BAT UCP1的表达较低。BAT(而不是WAT)UCP1的表达与年龄(r=−0.305)、体重(r=−0.374)、腰围(r=−0.296)、脂肪量(r=−0.388)和体重指数(r=−0.282)呈负相关。然而，分化的棕色脂肪细胞中的UCP1水平与上述任何测量结果都没有关联。在多元回归分析中，年龄是BAT UCP1高表达的唯一独立预测因素。有趣的是，在40岁的肥胖者中，BAT UCP1水平并没有降低。为了确定年轻肥胖者体内是否保留了BAT活性，我们对6名正常体重(BMI 22±1 kg/m2)和6名肥胖(BMI 32±1 kg/m2)年龄匹配(22±1岁)的青年肥胖者进行了18F-FDG-PET/MR扫描。体重组间BAT 18F-FDG摄取(标准摄取值5.1±0.5vs4.2±0.6g/mL)和摄取量(69±14vs72±32cm3)相似，但肥胖组胰岛素抵抗较大(空腹血糖5.5±0.2vs4.3±0.1 mmol/L，胰岛素11.9±1.3vs5.8±0.9mU/L，HOMA-IR 2.9±0.3vs1.1±0.2，游离脂肪酸465±78vs240±34µM，均P<)；0.05)，表明BAT摄取18F-FDG不受胰岛素抵抗的显著影响。总之，BAT UCP1在有不利心脏代谢危险因素的个体中表达减少，但这些受试者保留棕色前脂肪细胞，并在适当刺激后形成新的生热脂肪细胞。在年轻肥胖受试者中，UCP1的表达和BAT对冷诱导的18F-FDG的摄取保持不变。这些数据突出了BAT肿块扩张和激活作为一种治疗策略的治疗潜力，以改善肥胖导致的心脏代谢后果。演示文稿：2023年6月15日星期四
Disclosure: T. Kwok: None. L.E. Ramage: None. K.J. Suchacki: None. C. Gray: None. K. Alexandra: None. L.D. Boyle: None. R.K. Semple: None. S.I. Semple: None. T. MacGillivray: None. E.J. van Beek: None. S. Wakelin: None. R.H. Stimson: None. Brown adipose tissue (BAT) is a promising therapeutic target for obesity. 18F-Fluorodeoxyglucose positron emission tomography (18F-FDG PET) is the most commonly used imaging modality to quantify human BAT activity. 18F-FDG uptake may be reduced in obesity but insulin resistance has been suggested as a potential confounding factor. Uncoupling protein 1 (UCP1) is the key thermogenic protein in BAT and thus serves as a surrogate measure of BAT thermogenic capacity. We quantified UCP1 expression in paired BAT and white adipose tissue (WAT) samples from 141 patients undergoing elective neck surgery. UCP1 mRNA was quantified in whole tissue (n=53) and differentiated pre-adipocytes (n=88). Data are presented as mean ± SEM. Individuals with high UCP1 expression in whole BAT (>2 arbitrary units) were younger (44.2 ± 3.5 vs 55.7 ± 2.0 years) with lower BMI (26.5 ± 1.2 vs 30.1 ± 1.0kg/m2), waist circumference (87.9 ± 2.9 vs 101.1 ± 2.6cm), waist-hip ratio (0.86 ± 0.01 vs 0.92 ± 0.01), fat percentage (29.1 ± 2.6 vs 35.3 ± 1.7%), insulin resistance (HOMA-IR 1.44 ± 0.18 vs 2.69 ± 0.35), systolic (131 ± 6 vs 143 ± 4mmHg) and diastolic blood pressure (79 ± 3 vs 86 ± 2mmHg) (all P<0.05). BAT UCP1 expression was lower in subjects on beta-blockers or with existing hypertension. BAT (but not WAT) UCP1 expression correlated negatively with age (r=−0.305), weight (r=−0.374), waist circumference (r=−0.296), fat mass (r=−0.388) and BMI (r=−0.282) (all P<0.05). However, UCP1 levels in differentiated brown adipocytes were not associated with any of the above measurements. In multiple regression, age was the only independent predictor of high BAT UCP1 expression. Interestingly, BAT UCP1 levels were not reduced in obese subjects aged <40 years. To determine whether BAT activity was preserved in young obese subjects in vivo, we performed 18F-FDG-PET/MR scanning during mild cold exposure (16-17°C) in 6 normal weight (BMI 22 ± 1kg/m2) and 6 obese (BMI 32 ± 1kg/m2) age-matched (22 ± 1 years) subjects. BAT 18F-FDG uptake (standard uptake value 5.1 ± 0.5 vs 4.2 ± 0.6 g/mL) and volume (69 ± 14 vs 72 ± 32 cm3) were similar between weight groups, despite greater insulin resistance in obese subjects (fasting glucose 5.5 ± 0.2 vs 4.3 ± 0.1mmol/L, insulin 11.9 ± 1.3 vs 5.8 ± 0.9mU/L, HOMA-IR 2.9 ± 0.3 vs 1.1 ± 0.2, free fatty acids 465 ± 78 vs 240 ± 34µM, all P<0.05), suggesting that 18F-FDG uptake by BAT is not significantly affected by insulin resistance. In conclusion, BAT UCP1 expression is reduced in individuals with adverse cardiometabolic risk factors, but these subjects retain brown pre-adipocytes with the capacity to form new thermogenic adipocytes after appropriate stimulation. UCP1 expression and cold-induced 18F-FDG uptake by BAT is preserved in young obese subjects. These data highlight the therapeutic potential of BAT mass expansion and activation as a therapeutic strategy to ameliorate the cardiometabolic consequences of obesity. Presentation: Thursday, June 15, 2023