In this era of increased obesity and diabetes prevalence, the browning of white adipose tissue (WAT) has emerged as a promising therapeutic target to induce weight loss and improve insulin sensitivity in this population. The browning process entails a shift in the WAT from primarily storing excess energy to the dissipation of energy as heat. However, this idealistic view of WAT browning being the savior of the metabolic syndrome has been criticized by studies in burn and cancer patients that have shown browning to be detrimental rather than beneficial. In fact, in the context of hypermetabolic states, the browning of WAT has presented with substantial clinical adverse outcomes related to cachexia, hepatic steatosis, and muscle catabolism. Therefore, the previous thought construct of understanding browning as an all-beneficial physiologic event has now been met with skepticism. In this review, we focus on current knowledge of browning of WAT and its adverse metabolic alterations during hypermetabolic states. We also discuss the regulators and signaling pathways involved in the browning process and their potential for being targeted by new or existing drugs to inhibit or alleviate browning, potentially leading to decreased hypermetabolism and improved clinical outcomes. Lastly, the imminent clinical applications of pharmacological agents are explored in the perspective of attenuating WAT browning and its associated adverse side effects reported in burn patients.

中文翻译：

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驯服火焰：针对代谢亢进条件下的白色脂肪组织褐变


在这个肥胖和糖尿病患病率增加的时代，白色脂肪组织（WAT）的褐变已成为一个有前途的治疗目标，可诱导该人群减肥并提高胰岛素敏感性。褐变过程需要 WAT 从主要存储多余能量转变为以热量形式耗散能量。然而，这种认为 WAT 褐变是代谢综合征救世主的理想主义观点受到了对烧伤和癌症患者的研究的批评，这些研究表明褐变是有害的而不是有益的。事实上，在代谢亢进状态下，WAT 的褐变会带来与恶病质、肝脂肪变性和肌肉分解代谢相关的大量临床不良后果。因此，以前将褐变理解为一种有益的生理事件的思想结构现在遭到了怀疑。在这篇综述中，我们重点关注 WAT 褐变及其在代谢亢进状态下的不良代谢变化的最新知识。我们还讨论了褐变过程中涉及的调节因子和信号通路，以及它们成为新药或现有药物抑制或减轻褐变的潜力，从而可能导致代谢亢进的减少和临床结果的改善。最后，从减轻烧伤患者 WAT 褐变及其相关不良副作用的角度探讨了药物的临床应用。