Evidence map›Paper›PMID 28974562›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2018

Autophagy and mitochondrial biogenesis impairment contribute to age-dependent liver injury in experimental sepsis: dysregulation of AMP-activated protein kinase pathway.

Yu Inata, Satoshi Kikuchi, Ravi S Samraj, Paul W Hake, Michael O'Connor, John R Ledford, James O'Connor, Patrick Lahni, Vivian Wolfe, Giovanna Piraino and 1 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
3.6field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

34 citing papers in PubMed, 64 citations in OpenAlex.

  1. Research square · 2026
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  9. Targeting AMP-activated protein kinase in sepsis.Frontiers in endocrinology · 2024
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  18. Regulation of Phosphorylated State of NMDA Receptor by STEPAntioxidants (Basel, Switzerland) · 2021
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Yu InataDivision of Critical Care Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
Satoshi KikuchiDivision of Critical Care Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
Ravi S SamrajDivision of Critical Care Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
Paul W HakeDivision of Critical Care Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
Michael O'ConnorDivision of Critical Care Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
John R LedfordDivision of Critical Care Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
James O'ConnorDivision of Critical Care Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
Patrick LahniDivision of Critical Care Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
Vivian WolfeDivision of Critical Care Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
Giovanna PirainoDivision of Critical Care Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
Basilia ZingarelliDivision of Critical Care Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
University of Cincinnati · USCincinnati Children's Hospital Medical Center · US

Funding

Stem Cell/Organoid and Genome Editing CoreP30DK078392 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI Alexander Miethke · 2007 to 2026
$24.4M
PPARgamma and PPARgamma agonists in septic shockR01GM067202 · NIGMS · CINCINNATI CHILDRENS HOSP MED CTR · PI ZINGARELLI, BASILIA · 2003 to 2015
$3.9M
NIDDK NIH HHS P30 DK078392NIGMS NIH HHS R01 GM067202
6 · The paper itself

Abstract

Age is an independent risk factor of multiple organ failure in patients with sepsis. However, the age-related mechanisms of injury are not known. AMPK is a crucial regulator of energy homeostasis, which controls mitochondrial biogenesis by activation of peroxisome proliferator-activated receptor-γ coactivator-α (PGC-1α) and disposal of defective organelles by autophagy. We investigated whether AMPK dysregulation might contribute to age-dependent liver injury in young (2-3 mo) and mature male mice (11-13 mo) subjected to sepsis. Liver damage was higher in mature mice than in young mice and was associated with impairment of hepatocyte mitochondrial function, structure, and biogenesis and reduced autophagy. At molecular analysis, there was a time-dependent nuclear translocation of the active phosphorylated catalytic subunits AMPKα1/α2 and PGC-1α in young, but not in mature, mice after sepsis. Treatment with the AMPK activator 5-amino-4-imidazolecarboxamide riboside-1-β-d-ribofuranoside (AICAR) improved liver mitochondrial structure in both age groups compared with vehicle. In loss-of-function studies, young knockout mice with systemic deficiency of AMPKα1 exhibited greater liver injury than did wild-type mice after sepsis. Our study suggests that AMPK is important for liver metabolic recovery during sepsis. Although its function may diminish with age, pharmacological activation of AMPK may be of therapeutic benefit.-Inata, Y., Kikuchi, S., Samraj, R. S., Hake, P. W., O'Connor, M., Ledford, J. R., O'Connor, J., Lahni, P., Wolfe, V., Piraino, G., Zingarelli, B. Autophagy and mitochondrial biogenesis impairment contribute to age-dependent liver injury in experimental sepsis: dysregulation of AMP-activated protein kinase pathway.

Indexed as

AutophagyActive Transport, Cell NucleusAgingAminoimidazole CarboxamideAMP-Activated Protein KinasesAnimalsCell NucleusLiverMiceMice, KnockoutMitochondria, LiverRibonucleotidesSepsisAICA ribonucleotideAminoimidazole CarboxamideAMP-Activated Protein KinasesPrkaa1 protein, mousePrkaa2 protein, mouseRibonucleotidesAICARcecal ligation and punctureMODSPGC-1α

Identifiers

PMID28974562
PMCPMC5888394
OpenAlexW2761427496

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.