Taming the Flames: Targeting White Adipose Tissue Browning in Hypermetabolic Conditions

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.