Hepatic FGF21 preserves thermoregulation and cardiovascular function during bacterial inflammation

Area of Science:

• Metabolic regulation
• Infectious disease
• Endocrinology

Background:

• Sickness behaviors, such as anorexia, are conserved responses to infections.
• Inflammation-induced anorexia triggers metabolic changes critical for survival, varying by inflammation type.
• Fibroblast growth factor 21 (FGF21) plays a role in metabolic adaptation during infection.

Purpose of the Study:

• To investigate the role of hepatic-derived FGF21 in bacterial inflammation.
• To determine the mechanisms by which FGF21 promotes survival during sepsis.
• To identify the target tissues and pathways involved in FGF21-mediated responses.

Main Methods:

• Analysis of FGF21 levels in mice during bacterial inflammation.
• Assessment of survival rates in FGF21-deficient and wild-type mice.
• Investigation of FGF21 signaling pathways, including the role of β-Klotho (KLB).

Main Results:

• Circulating FGF21 is increased during bacterial inflammation and is hepatic-derived.
• FGF21 is required for survival, maintaining thermogenesis, energy expenditure, and cardiac function.
• FGF21 signaling via KLB is essential for bacterial sepsis survival, independent of known cold adaptation pathways.

Conclusions:

• Hepatic FGF21 is a critical mediator of survival during bacterial inflammation.
• FGF21's role in sepsis involves novel signaling pathways distinct from cold adaptation.
• Further research is needed to identify FGF21's specific target tissues in bacterial sepsis.