Brown fat fuels the fire in fever.

Abstract

Fever is a host-pathogen defense mechanism in which the immune system drives a physiologic increase in core body temperature. For over 50 years, it has been known that the temperature of brown adipose tissue (BAT) is increased during the febrile response. However, recent studies suggested that the primary thermogenic protein Uncoupling protein 1 in brown adipocytes does not contribute to fever induction in mice, casting doubt about the functional contribution of BAT to fever. In a new set of studies, Li et al. (2024) provide compelling evidence that fatty acid oxidation is markedly increased in BAT in a Salmonella infection model of fever and strongly suggest that metabolic adaptation in BAT may play a critical role in the febrile response. This article re-opens the debate about how thermogenic and metabolic programs in BAT contribute to fever and raises new questions about whether BAT contributes to host defense against pathogens.