Matches in SemOpenAlex for { <https://semopenalex.org/work/W1993769712> ?p ?o ?g. }
Showing items 1 to 70 of
70
with 100 items per page.
- W1993769712 endingPage "715" @default.
- W1993769712 startingPage "715" @default.
- W1993769712 abstract "<h3>Summary</h3> Reprogramming metabolism is of great therapeutic interest for reducing morbidity and mortality during sepsis-induced critical illness<sup>1</sup>. Disappointing results from randomized controlled trials targeting glutamine and antioxidant metabolism in patients with sepsis have begged for both identification of new metabolic targets, and a deeper understanding of the metabolic fate of glutamine at the systemic and tissue-specific manner<sup>2–4</sup>. In critically ill patients versus elective surgical controls, skeletal muscle transcriptional metabolic reprogramming is comprised of reduced expression of genes involved in mitochondrial metabolism, electron transport, and glutamate transport, with concomitant increases in glutathione cycling, glutamine, branched chain, and aromatic amino acid transport. To analyze putative interorgan communications during sepsis, we performed systemic and tissue specific metabolic phenotyping in a murine polymicrobial sepsis model, cecal ligation and puncture. In the setting of drastically elevated inflammatory cytokines, we observed >10% body weight loss, >50% reductions in oxygen consumption and carbon dioxide production, and near full suppression of voluntary activity for the 48 hours following sepsis as compared to sham-operated controls. We found increased correlations in the metabolome between liver, kidney, and spleen, with drastic loss of correlations between the heart and quadriceps metabolome and all other organs, pointing to a shared metabolic signature within vital abdominal organs, and unique metabolic signatures for skeletal and cardiac muscle during sepsis. A lowered GSH:GSSG and elevated AMP:ATP ratio in the liver underlie the significant upregulation of isotopically labeled glutamine’s contribution to TCA anaplerosis and glutamine-derived glutathione biosynthesis; meanwhile, the skeletal muscle and spleen were the only organs where glutamine’s contribution to the TCA cycle was significantly suppressed. These results highlight tissue-specific mitochondrial reprogramming, rather than global mitochondrial dysfunction, as a mechanistic consequence of sepsis. Using a multi-omic approach, we demonstrate a model by which sepsis-induced proteolysis fuels the liver’s production of anaplerotic substrates and the antioxidant glutathione to sustain tolerance to sepsis." @default.
- W1993769712 created "2016-06-24" @default.
- W1993769712 creator A5048850621 @default.
- W1993769712 date "1969-03-15" @default.
- W1993769712 modified "2023-09-26" @default.
- W1993769712 title "Bilateral tension pneumothorax in newborn." @default.
- W1993769712 doi "https://doi.org/10.1136/bmj.1.5645.715-c" @default.
- W1993769712 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1982713" @default.
- W1993769712 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/5774335" @default.
- W1993769712 hasPublicationYear "1969" @default.
- W1993769712 type Work @default.
- W1993769712 sameAs 1993769712 @default.
- W1993769712 citedByCount "1" @default.
- W1993769712 crossrefType "journal-article" @default.
- W1993769712 hasAuthorship W1993769712A5048850621 @default.
- W1993769712 hasBestOaLocation W19937697121 @default.
- W1993769712 hasConcept C104317684 @default.
- W1993769712 hasConcept C126322002 @default.
- W1993769712 hasConcept C127561419 @default.
- W1993769712 hasConcept C134018914 @default.
- W1993769712 hasConcept C135870905 @default.
- W1993769712 hasConcept C181199279 @default.
- W1993769712 hasConcept C2777477808 @default.
- W1993769712 hasConcept C2778384902 @default.
- W1993769712 hasConcept C2779349466 @default.
- W1993769712 hasConcept C515207424 @default.
- W1993769712 hasConcept C538909803 @default.
- W1993769712 hasConcept C55493867 @default.
- W1993769712 hasConcept C62231903 @default.
- W1993769712 hasConcept C71924100 @default.
- W1993769712 hasConcept C86803240 @default.
- W1993769712 hasConceptScore W1993769712C104317684 @default.
- W1993769712 hasConceptScore W1993769712C126322002 @default.
- W1993769712 hasConceptScore W1993769712C127561419 @default.
- W1993769712 hasConceptScore W1993769712C134018914 @default.
- W1993769712 hasConceptScore W1993769712C135870905 @default.
- W1993769712 hasConceptScore W1993769712C181199279 @default.
- W1993769712 hasConceptScore W1993769712C2777477808 @default.
- W1993769712 hasConceptScore W1993769712C2778384902 @default.
- W1993769712 hasConceptScore W1993769712C2779349466 @default.
- W1993769712 hasConceptScore W1993769712C515207424 @default.
- W1993769712 hasConceptScore W1993769712C538909803 @default.
- W1993769712 hasConceptScore W1993769712C55493867 @default.
- W1993769712 hasConceptScore W1993769712C62231903 @default.
- W1993769712 hasConceptScore W1993769712C71924100 @default.
- W1993769712 hasConceptScore W1993769712C86803240 @default.
- W1993769712 hasIssue "5645" @default.
- W1993769712 hasLocation W19937697121 @default.
- W1993769712 hasLocation W19937697122 @default.
- W1993769712 hasLocation W19937697123 @default.
- W1993769712 hasLocation W19937697124 @default.
- W1993769712 hasOpenAccess W1993769712 @default.
- W1993769712 hasPrimaryLocation W19937697121 @default.
- W1993769712 hasRelatedWork W2020449916 @default.
- W1993769712 hasRelatedWork W2025703417 @default.
- W1993769712 hasRelatedWork W2107729314 @default.
- W1993769712 hasRelatedWork W2132714283 @default.
- W1993769712 hasRelatedWork W2153965615 @default.
- W1993769712 hasRelatedWork W2157270415 @default.
- W1993769712 hasRelatedWork W2409608972 @default.
- W1993769712 hasRelatedWork W311287571 @default.
- W1993769712 hasRelatedWork W3137540029 @default.
- W1993769712 hasRelatedWork W4220896095 @default.
- W1993769712 hasVolume "1" @default.
- W1993769712 isParatext "false" @default.
- W1993769712 isRetracted "false" @default.
- W1993769712 magId "1993769712" @default.
- W1993769712 workType "article" @default.