Foti_2026_Adipocyte_15_2626121

Fever reflects a physiological rise in body temperature accompanied by elevated production of adrenaline. The increased body temperature in fever is caused by shivering thermogenesis in skeletal muscle and non-shivering thermogenesis in brown adipose tissue (BAT), the latter being mediated by uncoupled oxidation of free fatty acids (FFAs). We hypothesized that an acute temperature rise to 40 degreesC increases adrenalin-induced lipolysis in white adipocytes, thereby potentially providing FFAs as an energy substrate to sustain fever-induced thermogenesis in skeletal muscle and BAT. In 3T3-L1 and primary murine white adipocytes, isoproterenol-induced extracellular FFA accumulation was significantly increased at 40 degreesC compared to 37 degreesC. In contrast, isoproterenol-induced increase in extracellular glycerol concentrations and the protein levels of phosphorylated hormone sensitive lipase were comparable at both temperatures, suggesting a similar degree of lipolysis. Moreover, incubation at 40 degreesC did neither increase isoproterenol-induced oxygen consumption nor intracellular FFA concentrations, indicating that the elevated extracellular FFA accumulation was not due to reduced intracellular consumption. Conversely, isoproterenol blunted FFA uptake into adipocytes to a significantly higher extent at 40 degreesC compared to 37 degreesC. Hence, an acute temperature rise to 40 degreesC reduces FFA uptake into white adipocytes, thereby increasing extracellular FFA availability.