# An acute temperature rise to 40°C inhibits free fatty acid uptake into white adipocytes

## TL;DR

A sudden rise in body temperature to 40°C reduces free fatty acid uptake into white fat cells, increasing their availability for energy use during fever.

## Contribution

The study reveals a novel mechanism by which elevated body temperature during fever affects free fatty acid dynamics in white adipocytes.

## Key findings

- An acute temperature rise to 40°C increases extracellular free fatty acid accumulation in white adipocytes.
- FFA uptake into white adipocytes is significantly reduced at 40°C compared to 37°C.
- The temperature increase does not affect lipolysis or intracellular FFA consumption.

## Abstract

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°C 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°C compared to 37°C. 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°C 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°C compared to 37°C. Hence, an acute temperature rise to 40°C reduces FFA uptake into white adipocytes, thereby increasing extracellular FFA availability.