Brown adipose tissue (BAT) displays the unique capacity to generate heat through uncoupled oxidative phosphorylation that makes it a very attractive therapeutic target for cardiometabolic diseases. Here, we review BAT cellular metabolism, its regulation by the central nervous and endocrine systems and circulating metabolites, the plausible roles of this tissue in human thermoregulation, energy balance, and cardiometabolic disorders, and the current knowledge on its pharmacological stimulation in humans. The current definition and measurement of BAT in human studies relies almost exclusively on BAT glucose uptake from positron emission tomography with 18F-fluorodeoxiglucose, which can be dissociated from BAT thermogenic activity, as for example in insulin-resistant states. The most important energy substrate for BAT thermogenesis is its intracellular fatty acid content mobilized from sympathetic stimulation of intracellular triglyceride lipolysis. This lipolytic BAT response is intertwined with that of white adipose (WAT) and other metabolic tissues, and cannot be independently stimulated with the drugs tested thus far. BAT is an interesting and biologically plausible target that has yet to be fully and selectively activated to increase the body's thermogenic response and shift energy balance. The field of human BAT research is in need of methods able to directly, specifically, and reliably measure BAT thermogenic capacity while also tracking the related thermogenic responses in WAT and other tissues. Until this is achieved, uncertainty will remain about the role played by this fascinating tissue in human cardiometabolic diseases.

中文翻译：

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棕色脂肪组织——转化的视角。

棕色脂肪组织 (BAT) 显示出通过非偶联氧化磷酸化产生热量的独特能力，这使其成为心脏代谢疾病非常有吸引力的治疗靶点。在这里，我们回顾了 BAT 细胞代谢、它对中枢神经和内分泌系统以及循环代谢物的调节、该组织在人体体温调节、能量平衡和心脏代谢紊乱中的合理作用，以及目前关于它在人体中的药理刺激的知识。目前在人类研究中 BAT 的定义和测量几乎完全依赖于使用 18F-氟脱氧葡萄糖的正电子发射断层扫描对 BAT 葡萄糖的摄取，这可以从 BAT 产热活动中分离出来，例如在胰岛素抵抗状态下。BAT 产热最重要的能量底物是其细胞内脂肪酸含量，其来自细胞内甘油三酯脂肪分解的交感神经刺激。这种脂解 BAT 反应与白色脂肪 (WAT) 和其他代谢组织的反应交织在一起，并且不能用迄今为止测试的药物独立刺激。BAT 是一个有趣且生物学上合理的目标，尚未被完全和选择性地激活以增加身体的产热反应和改变能量平衡。人类 BAT 研究领域需要能够直接、具体、可靠地测量 BAT 产热能力，同时跟踪 WAT 和其他组织中相关产热反应的方法。在实现这一目标之前，