University/BHF Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK.
Eur J Endocrinol. 2021 May 4;184(6):R243-R259. doi: 10.1530/EJE-20-1439.
Excessive accumulation of white adipose tissue leads to obesity and its associated metabolic health consequences such as type 2 diabetes and cardiovascular disease. Several approaches to treat or prevent obesity including public health interventions, surgical weight loss, and pharmacological approaches to reduce caloric intake have failed to substantially modify the increasing prevalence of obesity. The (re-)discovery of active brown adipose tissue (BAT) in adult humans approximately 15 years ago led to a resurgence in research into whether BAT activation could be a novel therapy for the treatment of obesity. Upon cold stimulus, BAT activates and generates heat to maintain body temperature, thus increasing energy expenditure. Activation of BAT may provide a unique opportunity to increase energy expenditure without the need for exercise. However, much of the underlying mechanisms surrounding BAT activation are still being elucidated and the effectiveness of BAT as a therapeutic target has not been realised. Research is ongoing to determine how best to expand BAT mass and activate existing BAT; approaches include cold exposure, pharmacological stimulation using sympathomimetics, browning agents that induce formation of thermogenic beige adipocytes in white adipose depots, and the identification of factors secreted by BAT with therapeutic potential. In this review, we discuss the caloric capacity and other metabolic benefits from BAT activation in humans and the role of metabolic tissues such as skeletal muscle in increasing energy expenditure. We discuss the potential of current approaches and the challenges of BAT activation as a novel strategy to treat obesity and metabolic disorders.
白色脂肪组织过度积累会导致肥胖及其相关的代谢健康问题，如 2 型糖尿病和心血管疾病。几种治疗或预防肥胖的方法，包括公共卫生干预、减肥手术和减少热量摄入的药物方法，都未能显著改变肥胖的不断上升趋势。大约 15 年前，人们重新发现了成年人体内活跃的棕色脂肪组织（BAT），这促使人们对 BAT 的激活是否可以成为治疗肥胖的一种新疗法进行了重新研究。在受到寒冷刺激时，BAT 会激活并产生热量以维持体温，从而增加能量消耗。激活 BAT 可能为增加能量消耗提供了一个独特的机会，而无需进行运动。然而，围绕 BAT 激活的许多潜在机制仍在阐明之中，BAT 作为治疗靶点的有效性尚未实现。目前正在进行研究，以确定如何最好地扩大 BAT 质量并激活现有的 BAT；方法包括冷暴露、使用拟交感神经药的药物刺激、诱导白色脂肪组织中形成产热米色脂肪细胞的褐色化剂，以及鉴定具有治疗潜力的 BAT 分泌因子。在这篇综述中，我们讨论了 BAT 激活在人类中的热量容量和其他代谢益处，以及代谢组织（如骨骼肌）在增加能量消耗方面的作用。我们讨论了当前方法的潜力和 BAT 激活作为治疗肥胖和代谢紊乱的新策略所面临的挑战。
