Fueling or Fighting Cancer? The Thermogenic Paradox of Brown Adipose Tissue

The global rise in obesity and metabolic syndrome has intensified interest in brown adipose tissue (BAT) as a regulator of energy metabolism and potential modulator of cancer risk. BAT-mediated thermogenesis and the browning of white adipose tissue (WAT) confer metabolic benefits that may reduce oncogenic susceptibility. However, emerging evidence reveals a paradoxical role for BAT in cancer progression, where tumor-induced thermogenic activation contributes to cancer-associated cachexia (CAC). This review article examines the cellular, molecular, and translational dimensions of this “thermogenic paradox”. A narrative synthesis was performed using literature from 2000 to 2025 retrieved from PubMed, Scopus, Web of Science, and Google Scholar. Peer-reviewed studies examining the molecular, genetic, and metabolic mechanisms linking BAT or adipose browning to carcinogenesis, obesity-related cancers, and CAC were included. Thematic integration emphasized regulatory pathways, endocrine signaling, and therapeutic implications. Adaptive browning, regulated by transcriptional drivers such as PRDM16, PPARγ, and PGC1-α, mitigates metabolic inflammation, enhances insulin sensitivity, and may exert tumor-suppressive effects. In contrast, tumor-secreted factors including parathyroid hormone-related protein (PTHrP) and interleukin-6 aberrantly induce uncoupling protein 1 (UCP1) expression and β3-adrenergic signaling, driving lipolysis and energy wasting in CAC. The dualistic effects of BAT underscore its context-dependent influence on cancer biology. BAT exemplifies a metabolic continuum between protection and pathology. Clarifying its regulatory mechanisms may inform precision therapies and integrated metabolic-oncology interventions, particularly relevant to low- and middle-income countries facing the double burden of obesity and cachexia.