Details

Autor(en) / Beteiligte

• Luan, Harding H.
• Wang, Andrew
• Hilliard, Brandon K.
• Carvalho, Fernando
• Rosen, Connor E.
• Ahasic, Amy M.
• Herzog, Erica L.
• Kang, Insoo
• Pisani, Margaret A.
• Yu, Shuang
• Zhang, Cuiling
• Ring, Aaron M.
• Young, Lawrence H.
• Medzhitov, Ruslan

Titel

GDF15 Is an Inflammation-Induced Central Mediator of Tissue Tolerance

Ist Teil von

• Cell, 2019-08, Vol.178 (5), p.1231-1244.e11

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• Growth and differentiation factor 15 (GDF15) is an inflammation-associated hormone with poorly defined biology. Here, we investigated the role of GDF15 in bacterial and viral infections. We found that inflammation induced GDF15, and that GDF15 was necessary for surviving both bacterial and viral infections, as well as sepsis. The protective effects of GDF15 were largely independent of pathogen control or the magnitude of inflammatory response, suggesting a role in disease tolerance. Indeed, we found that GDF15 was required for hepatic sympathetic outflow and triglyceride metabolism. Failure to defend the lower limit of plasma triglyceride levels was associated with impaired cardiac function and maintenance of body temperature, effects that could be rescued by exogenous administration of lipids. Together, we show that GDF15 coordinates tolerance to inflammatory damage through regulation of triglyceride metabolism. [Display omitted] •GDF15 is induced upon bacterial and viral inflammation•GDF15 promotes metabolic adaptation to systemic inflammation•GDF15 stimulates hepatic triglyceride export via beta-adrenergic signaling•Maintenance of triglyceride levels during acute inflammation is cardioprotective The hormone GDF15 promotes tolerance and survival during conditions of infection and sepsis by modulating systemic levels of plasma triglycerides.