Enhanced lipid utilization is coupled to the sickness responses triggered by lipopolysaccharide

Sickness symptoms exerted via inflammatory responses occur in several infectious and chronic diseases. A growing body of evidence suggests that altered nutrient availability and metabolism are tightly coupled to inflammatory processes. However, the relationship between metabolic shifts and the development of the sickness response has not been explored fully. Therefore, we aimed to evaluate metabolic phenotypes with a mouse model showing sickness symptoms via systemic administration of lipopolysaccharide (LPS) in the present study. LPS injection elevated the lipid utilization and circulating levels of fatty acids. It also increased the levels of β-hydroxybutyric acid, a ketone body produced from fatty acids. We confirmed the functional connectivity between nutrient utilization and inflammatory responses and demonstrated enhanced lipid utilization in the hypothalamus providing insights into hypothalamic control of sickness responses. Collectively, these findings could help develop new therapeutic strategies to treat patients with severe sickness symptoms associated with infectious and chronic human diseases.