Imperial College School of Medicine, Imperial College London, London, UK.
Section of Endocrinology and Investigative Medicine, Imperial College London, London, UK.
Diabetes Metab Res Rev. 2023 Jan;39(1):e3594. doi: 10.1002/dmrr.3594. Epub 2022 Nov 22.
Approximately 30% of the global population is affected by obesity. Traditional non-surgical measures for weight loss have limited efficacy and tolerability. Therefore, there is a need for novel, effective therapies. Brown adipose tissue (BAT) has been implicated in physiological energy expenditure, indicating that it could be targeted to achieve weight loss in humans. The use of F-fluorodeoxyglucose ( F-FDG) positron emission tomography-computed tomography-(PET-CT) imaging has enabled the discovery of functionally active BAT in the supraclavicular, subclavian, and thoracic spine regions of human adults. This review aims to discuss the reasons behind the renewed interest in BAT, assess whether it is metabolically important in humans, and evaluate its feasibility as a therapeutic target for treating obesity.
PubMed Central, Europe PMC, Medline.
In vivo studies have shown that BAT activity is regulated by thyroid hormones and the sympathetic nervous system. Furthermore, BAT uniquely contains uncoupling protein 1 (UCP1) that is largely responsible for non-shivering thermogenesis. Cold exposure can increase BAT recruitment through the browning of white adipose tissue (WAT); however, this technique has practical limitations that may preclude its use. Currently available medicines for humans, such as the β3-adrenergic receptor agonist mirabegron or the farnesoid X receptor agonist obeticholic acid, have generated excitement, although adverse effects are a concern. Capsinoids represent a tolerable alternative, which require further investigation.
The use of currently available BAT-activating agents alone is unlikely to achieve significant weight loss in humans. A combination of BAT activation with physical exercise and modern, successful dietary strategies represents a more realistic option.
全球约有 30%的人口受到肥胖的影响。传统的非手术减肥措施疗效和耐受性有限。因此,需要新的、有效的治疗方法。棕色脂肪组织(BAT)与生理能量消耗有关,这表明它可以作为靶点,以实现人类减肥。使用 F-氟脱氧葡萄糖( F-FDG)正电子发射断层扫描-计算机断层扫描-(PET-CT)成像已能发现成人锁骨上、锁骨下和胸椎区域功能活跃的 BAT。本综述旨在讨论 BAT 重新受到关注的原因,评估其在人类中的代谢重要性,并评估其作为肥胖治疗靶点的可行性。
PubMed Central、Europe PMC、Medline。
体内研究表明,BAT 活性受甲状腺激素和交感神经系统调节。此外,BAT 独特地含有解偶联蛋白 1(UCP1),主要负责非寒战产热。冷暴露可通过白色脂肪组织(WAT)的“褐变”增加 BAT 的募集;然而,这种技术有实际限制,可能使其无法使用。目前可用于人类的药物,如β3-肾上腺素能受体激动剂米拉贝隆或法尼醇 X 受体激动剂奥贝胆酸,引起了人们的兴趣,尽管不良反应令人担忧。辣椒素代表一种可耐受的替代物,需要进一步研究。
单独使用目前可用的激活 BAT 的药物不太可能使人类体重显著减轻。将 BAT 激活与体育锻炼和现代、成功的饮食策略相结合,是一种更现实的选择。