Introduction: Brown adipose tissue (BAT) combusts lipids and glucose to generate heat. Via this process of non-shivering thermogenesis, BAT plays a pivotal role in thermoregulation in cold environments, but its contribution to immune-induced fever is less clear. 

Methods:  Male APOE*3-Leiden.CETP mice, a well-known animal model for human-like lipoprotein metabolism, were given an intraperitoneal injection of Salmonella Typhimurium (S.tm). Energy expenditure and substrate utilization, plasma lipid levels, fatty acid uptake by adipose tissues, and lipid content and thermogenic markers in adipose tissues were examined.

Results:  S.tm infection led to a set of characteristic symptoms, including elevated body temperature, decreased body weight, and reduced physical activity and food intake. Whole-body energy expenditure experienced was significantly decreased 72 hours post-infection, but fat oxidation was increased and accompanied by a substantial reduction in plasma triglyceride (TG) levels. S.tm infection strongly increased uptake of fatty acids from TG-rich lipoproteins (TRLs) by BAT, which showed a positive correlation body temperature in infected mice. Upon histological examination of the tissue, elevated levels of tyrosine hydroxylase were observed, indicative of stimulated sympathetic activity. In addition, uncoupling protein 1 (UCP-1) protein levels were found to be increased, while lipid content was reduced. Furthermore, browning of white adipose tissue was observed, evidenced by a modest increase in TG-derived fatty acid uptake, the presence of multilocular cells, and an induction of UCP-1 expression.

Conclusion: We proposed that BAT, or adipose tissue thermogenesis in general is involved in the maintenance of elevated body temperature caused by S.tm infection.

Keyword: Brown adipose tissue; Non-shivering thermogenesis; fever; Lipoprotein metabolism; Salmonella Typhimurium