Department of Human Biology, School for Nutrition and Toxicology and Metabolism - NUTRIM, Maastricht University, Maastricht, The Netherlands.
PLoS One. 2011 Feb 24;6(2):e17247. doi: 10.1371/journal.pone.0017247.
Cold-stimulated adaptive thermogenesis in brown adipose tissue (BAT) to increase energy expenditure is suggested as a possible therapeutic target for the treatment of obesity. We have recently shown high prevalence of BAT in adult humans, which was inversely related to body mass index (BMI) and body fat percentage (BF%), suggesting that obesity is associated with lower BAT activity. Here, we examined BAT activity in morbidly obese subjects and its role in cold-induced thermogenesis (CIT) after applying a personalized cooling protocol. We hypothesize that morbidly obese subjects show reduced BAT activity upon cold exposure.
After applying a personalized cooling protocol for maximal non-shivering conditions, BAT activity was determined using positron-emission tomography and computed tomography (PET-CT). Cold-induced BAT activity was detected in three out of 15 morbidly obese subjects. Combined with results from lean to morbidly obese subjects (n = 39) from previous study, the collective data show a highly significant correlation between BAT activity and body composition (P<0.001), respectively explaining 64% and 60% of the variance in BMI (r = 0.8; P<0.001) and BF% (r = 0.75; P<0.001). Obese individuals demonstrate a blunted CIT combined with low BAT activity. Only in BAT-positive subjects (n = 26) mean energy expenditure was increased significantly upon cold exposure (51.5±6.7 J/s versus 44.0±5.1 J/s, P = 0.001), and the increase was significantly higher compared to BAT-negative subjects (+15.5±8.9% versus +3.6±8.9%, P = 0.001), indicating a role for BAT in CIT in humans.
This study shows that in an extremely large range of body compositions, BAT activity is highly correlated with BMI and BF%. BAT-positive subjects showed higher CIT, indicating that BAT is also in humans involved in adaptive thermogenesis. Increasing BAT activity could be a therapeutic target in (morbid) obesity.
冷刺激棕色脂肪组织(BAT)产生适应性产热以增加能量消耗,这被认为是治疗肥胖症的一种可能的治疗靶点。我们最近发现,成年人体内存在大量的 BAT,其与体重指数(BMI)和体脂百分比(BF%)呈负相关,这表明肥胖与较低的 BAT 活性有关。在这里,我们通过应用个性化冷却方案,检查了病态肥胖患者的 BAT 活性及其在冷诱导产热(CIT)中的作用。我们假设病态肥胖患者在受到寒冷刺激时会表现出 BAT 活性降低。
在应用最大非颤抖条件下的个性化冷却方案后,使用正电子发射断层扫描和计算机断层扫描(PET-CT)来确定 BAT 活性。在 15 名病态肥胖患者中,有 3 名患者检测到冷诱导 BAT 活性。结合之前研究中从瘦到病态肥胖患者的结果(n=39),集体数据显示 BAT 活性与身体成分之间存在高度显著的相关性(P<0.001),分别解释了 BMI(r=0.8;P<0.001)和 BF%(r=0.75;P<0.001)变异的 64%和 60%。肥胖个体表现出 CIT 减弱和 BAT 活性降低。只有在 BAT 阳性患者(n=26)中,冷暴露时平均能量消耗显著增加(51.5±6.7 J/s 与 44.0±5.1 J/s,P=0.001),与 BAT 阴性患者相比,增加幅度显著更高(+15.5±8.9%与+3.6±8.9%,P=0.001),表明 BAT 在人类 CIT 中发挥作用。
本研究表明,在极其广泛的身体组成范围内,BAT 活性与 BMI 和 BF%高度相关。BAT 阳性患者表现出更高的 CIT,表明 BAT 在人类中也参与适应性产热。增加 BAT 活性可能成为(病态)肥胖症的治疗靶点。