Brown fat is emerging as an interesting and promising target for therapeutic intervention in obesity and metabolic disease. Activation of brown fat in humans is associated with marked improvement in metabolic parameters such as levels of free fatty acids and insulin sensitivity. Skeletal muscle is another important organ for thermogenesis, with the capacity to induce energy-consuming futile cycles. In this Review, we focus on how these two major thermogenic organs — brown fat and muscle — act and cooperate to maintain normal body temperature. Moreover, in the light of disease-relevant mechanisms, we explore the molecular pathways that regulate thermogenesis in brown fat and muscle. Brown adipocytes possess a unique cellular mechanism to convert chemical energy into heat: uncoupling protein 1 (UCP1), which can short-circuit the mitochondrial proton gradient. However, recent research demonstrates the existence of several other energy-expending 'futile' cycles in both adipocytes and muscle, such as creatine and calcium cycling. These mechanisms can complement or even substitute for UCP1-mediated thermogenesis. Moreover, they expand our view of cold-induced thermogenesis from a special feature of brown adipocytes to a more general physiological principle. Finally, we discuss how thermogenic mechanisms can be exploited to expend energy and hence offer new therapeutic opportunities.

褐色脂肪正在成为肥胖和代谢性疾病治疗干预中一个有趣且有希望的目标。人体内棕色脂肪的活化与代谢参数（例如游离脂肪酸水平和胰岛素敏感性）的显着改善有关。骨骼肌是生热的另一个重要器官，具有诱导耗能的无用周期的能力。在本综述中，我们重点介绍这两个主要的产热器官-棕色脂肪和肌肉-如何发挥作用并相互配合以维持正常的体温。此外，根据与疾病相关的机制，我们探讨了调节棕色脂肪和肌肉生热的分子途径。棕色脂肪细胞具有将化学能转化为热量的独特细胞机制：解偶联蛋白1（UCP1），这会缩短线粒体质子梯度。但是，最近的研究表明，脂肪细胞和肌肉中还存在其他一些耗能的“无效”循环，例如肌酸和钙循环。这些机制可以补充甚至替代UCP1介导的生热作用。此外，他们将我们对冷诱导产热的观点从棕色脂肪细胞的特殊功能扩展到了更一般的生理原理。最后，我们讨论如何利用产热机理来消耗能量，从而提供新的治疗机会。这些机制可以补充甚至替代UCP1介导的生热作用。此外，他们将我们对冷诱导产热的观点从棕色脂肪细胞的特殊功能扩展到了更一般的生理原理。最后，我们讨论如何利用产热机理来消耗能量，从而提供新的治疗机会。这些机制可以补充甚至替代UCP1介导的生热作用。此外，他们将我们对冷诱导产热的观点从棕色脂肪细胞的特殊功能扩展到了更一般的生理原理。最后，我们讨论如何利用产热机理来消耗能量，从而提供新的治疗机会。