TY - JOUR
T1 - Opposing Effects of Fasting Metabolism on Tissue Tolerance in Bacterial and Viral Inflammation
AU - Wang, Andrew
AU - Huen, Sarah
AU - Luan, Harding H.
AU - Yu, Shuang
AU - Zhang, Cuiling
AU - Gallezot, Jean Dominique
AU - Booth, Carmen J.
AU - Medzhitov, Ruslan
N1 - Funding Information:
We thank members of the R.M. lab for helpful discussions, Marya Shanabrough and Tamas Horvath for help with processing of brain specimens, and David Mangelsdorf and Steven Kliewer for making available the Fgf21 −/− mice. This study was supported by the HHMI, Else Kröner Fresenius Foundation, The Blavatnik Family Foundation, and grants from the NIH (AI046688, AI089771, and CA157461). A.W. was supported by NIH grant T32 AR07107-39. S.C.H. was supported by American Heart Association grant 13FTF17070000. H.H.L. was supported by the Gruber Science Fellowship. Plasma creatinine was processed through the Yale George M. O’Brien Kidney Center, NIH grant P30-DK079310. Preparation of histology sections were performed by the Yale Research Pathology and Histology Core.
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/9/8
Y1 - 2016/9/8
N2 - Acute infections are associated with a set of stereotypic behavioral responses, including anorexia, lethargy, and social withdrawal. Although these so-called sickness behaviors are the most common and familiar symptoms of infections, their roles in host defense are largely unknown. Here, we investigated the role of anorexia in models of bacterial and viral infections. We found that anorexia was protective while nutritional supplementation was detrimental in bacterial sepsis. Furthermore, glucose was necessary and sufficient for these effects. In contrast, nutritional supplementation protected against mortality from influenza infection and viral sepsis, whereas blocking glucose utilization was lethal. In both bacterial and viral models, these effects were largely independent of pathogen load and magnitude of inflammation. Instead, we identify opposing metabolic requirements tied to cellular stress adaptations critical for tolerance of differential inflammatory states.
AB - Acute infections are associated with a set of stereotypic behavioral responses, including anorexia, lethargy, and social withdrawal. Although these so-called sickness behaviors are the most common and familiar symptoms of infections, their roles in host defense are largely unknown. Here, we investigated the role of anorexia in models of bacterial and viral infections. We found that anorexia was protective while nutritional supplementation was detrimental in bacterial sepsis. Furthermore, glucose was necessary and sufficient for these effects. In contrast, nutritional supplementation protected against mortality from influenza infection and viral sepsis, whereas blocking glucose utilization was lethal. In both bacterial and viral models, these effects were largely independent of pathogen load and magnitude of inflammation. Instead, we identify opposing metabolic requirements tied to cellular stress adaptations critical for tolerance of differential inflammatory states.
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U2 - 10.1016/j.cell.2016.07.026
DO - 10.1016/j.cell.2016.07.026
M3 - Article
C2 - 27610573
AN - SCOPUS:84986253848
SN - 0092-8674
VL - 166
SP - 1512-1525.e12
JO - Cell
JF - Cell
IS - 6
ER -