Immune‐Induced Fever and Psychogenic Hyperthermia Can Occur Independently of Uncoupling Protein 1‐Mediated Brown Adipose Tissue Thermogenesis

ABSTRACT Aim Brown adipose tissue thermogenesis is widely considered an important effector mechanism in fever and emotionally induced hyperthermia (psychogenic fever), and increases in interscapular temperature are commonly interpreted as evidence of brown adipose tissue activation. Yet direct evidence for this interpretation remains limited and conflicting. Here, we tested these assumptions using complementary genetic and surgical approaches in rats. Methods We generated uncoupling protein 1 knockout rats, in which canonical brown adipose tissue thermogenesis is abolished, and examined body temperature responses to systemic inflammation induced by lipopolysaccharide and to emotional stressors, including restraint and cage exchange. In separate experiments, interscapular brown adipose tissue was surgically removed in wild‐type rats. Results Despite profound impairment of cold‐ and β ₃ ‐adrenergic‐induced thermogenesis, uncoupling protein 1 deletion did not affect lipopolysaccharide‐ or stress‐induced increases in core or interscapular temperature. Likewise, removal of interscapular brown adipose tissue did not alter the interscapular temperature response. Thus, increases in interscapular temperature occurred in the absence of both uncoupling protein 1 and interscapular brown adipose tissue. Consistent with these findings, immune challenge and emotional stress induced little or no change in thermogenic gene expression and had minimal effects on tissue mass, in contrast to robust activation by β ₃ ‐adrenergic stimulation. Conclusion Fever and psychogenic hyperthermia in rats do not require uncoupling protein 1‐mediated brown adipose tissue thermogenesis. Furthermore, increases in interscapular temperature are not necessarily indicative of brown adipose tissue thermogenesis, challenging a widely held interpretation of these phenomena.