Disease-associated adipose browning: current evidence and perspectives

Brown and beige adipose tissue represent evolutionary adaptations in mammals, functioning as specialized thermogenic organs to maintain body temperature. Over the past two decades, researches have demonstrated that white adipose tissue (WAT) browning is an effective strategy to enhance energy expenditure. However, a growing body of evidence indicates that the browning process frequently occurs in a variety of chronic disease states, though its pathophysiological significance remains unclear. This review summarized evidence of pathological browning observed in human diseases and animal models, including breast cancer, colorectal cancer (CRC), clear cell renal cell carcinoma (ccRCC), kidney health, burn injury, atherosclerotic, SARS-CoV-2 and sepsis. Despite distinct pathological contexts, adipose tissue browning is consistently observed. This suggests that browning may not simply serve its classical metabolically protective role, but instead reflect an atypical response to pathological stress. It is currently unclear whether this is a compensatory mechanism by the organism in a diseased state or merely a byproduct of the disease process. Whether this response is adaptive or a cause of disease progression remains unresolved. Future research should therefore focus on identifying the triggers and functional outcomes of pathological browning to better understand adipocyte plasticity and its role in disease progression.