Glucose - effects on survival in Listeria and influenza infection

[2020-07-03]
Presentation by Ruslan Medzhitov from 2018 titled "Inflammation and Disease Tolerance: Surviving Acute Illness"
1:25 cost of inflammation and cost vs. benefit trade-off
4:01 sickness behaviors, includes loss of appetite - observed in all animals including insects 
5:10 Decreased Food Intake After Listeria Infection - disease induced anorexia 
6:32 Anorexia Protects Against Listeria Infection (survival rate) 
7:43 Glucose is Sufficient for Lethality in Listeria Infection - even at only 2% of normal caloric intake 8:26 2DG (inhibits metabolism of glucose) increased survivorship (100% survival vs. 50% without 2DG) 
9:06 Effects of Feeding on Sepsis Survival - sepsis model using lipopolysaccharide (LPS) injection - same results found for feeding, glucose and 2DG experiments 
11:10 Effects of Glucose in LPS Sepsis is Independent of Magnitude of Inflammation 
11:48 Mechanism for Glucose-mediated Death in Bacterial Inflammation - review of fasting metabolism - PPAR alpha, ketogenesis, FGF21
14:18 Glucose Supplementation Suppresses LPS-induced Lypolysis and Ketogenesis
15:09 PPAR alpha and Ketogenic Program are Required for Surviving Bacterial Inflammation - PPARa and FGF21 and necessary for survival 
16:09 LPS sepsis induced oxidative stress in midbrain - incleased by glucose and decreased by 2DG ; increase in glucose uptake in midbrain shown on PET scan 
16:53 Death from LPS sepsis is preceded by convulsions ; can anti-epileptics prevent death by LPS sepsis? 
17:21 anti-epileptic drug valpoic acid rescues mice from LPS sepsis death, but not Keppra 
17:44 Valproic acid protects / 2dg does not protect in PPAR alpla knockout mice 
18:30 Summary of Part 1 - ketones and valproic acid acting as HDAC inhibitors 
20:20 Critical Role of Glucose Maintenance in Bacterial Sepsis - too little glucose also causes increased mortality
21:28 How does Feeding Affect Viral Inflammation? - mouse model of influenza infection
22:24 Feeding is Protective in Influenza Infection 
22:41 Glucose Partially Protects Against Mortality in Influenza Infection - "the rest of the protection is provided by sodium" 
22:57 Inhibition of Glucose Utilization is Lethal in Influenza Infection - (inhibited by 2DG)
23:13 Inhibiting Glucose Does not Affect Lung Pathology in [flu] 
23:47 Effect if Glucose Inhibition on [flu] Independent of [degree of] Inflammation and Viral Burden 24:20 Death from viral inflammation due to reduction in autonomic function; PET scan shows glucose preferentially taken up in brain stem 
25:04 Viral Infection and ER (Endoplasmic Reticulum) Stress - UPR > CHOP (Ddit3) > apoptosis - lack of glucose for protein glycosylation can cause ER stress 
26:35 Inhibition of Glucose Utilization in the Context of Viral Inflammation Induces CHOP in the Brain Stem - Poly(I:C) - mimics viral inflammation 
27:09 CHOP Deficiency is Sufficient to Protect Against POLY(I:C) + 2DG Mortality 
28:02 Summary Part II

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