Cell - 8 September 2016

monitoring (body temperature, blood O 2 saturation, respiratory
rate, and heart rate) in endotoxemic mice treated with PBS,
glucose, or 2DG 24 hr post-LPS injection and found that 2DG-
treated mice maintained their body temperature significantly
better than glucose- and PBS-treated mice (Figure S2C). To
assess other evidence of end-organ damage, we measured
plasma markers of tissue injury (troponin-I, alanine aminotrans-
ferase, and creatinine), which were largely unchanged between

treatments, with the exception that glucose-treated mice had

higher levels of plasma creatinine (Figure S2D). Finally, detailed

histopathologic analysis of H&E-stained slides of brain, heart,

lung, liver, kidney, pancreas, stomach, bone marrow, thymus,

and spleen was performed to identify any pathologic changes,

including edema, hemorrhage, inflammation, necrosis, and

apoptosis. The only difference in histopathologic changes was

a decreased presence of dark, shrunken neurons in the brains

Figure 2. Glucose Caloric Supplementation during LPS Sepsis Worsens Survival, whereas 2DG Promotes Survival
(A and B) Survival after 15 mg/kg IP LPS and PO gavage with food, glucose, olive oil, casein, or PBS vehicle. PO PBS n = 10; PO food n = 10 (p = 0.0002 versus PO
PBS); PO glucose n = 8 (p < 0.0001 versus PO PBS); no gavage n = 10 (p = 0.0679 versus PO PBS). (A) is a subset of (B), separated for clarity (the same PBS-
treated, food-treated, and no gavage groups are shown in A and B).
(C) Survival after 15 mg/kg IP LPS and PO gavage with food with IP injections of PBS or 2DG. p = 0.0433.
(D–F) Mice were given 15 mg/kg IP LPS and then treated with IP PBS, glucose, or 2DG. (D) Survival after LPS and indicated treatments is shown. IP PBS n = 16;IP
glucose n = 10 (p < 0.0001 versus IP PBS); IP 2DG n = 10 (p = 0.01 versus IP PBS). (E) Plasma TNFaand IL-6 are shown. n = 5–10/group. (F) Liver mRNA
expression 4 hr after LPS and treatment with PBS (LPS-PBS), glucose (LPS-glucose), and 2DG (LPS-2DG) compared to PBS alone is shown. n = 3–5/group.
Data are represented as mean±SEM. See alsoFigure S2.

Cell 166 , 1512–1525, September 8, 2016 1515