Evidence map›Paper›PMID 39932791›Full record

ArticleJCI insight2025

Loss of long-chain acyl-CoA dehydrogenase protects against acute kidney injury.

Takuto Chiba, Akira Oda, Yuxun Zhang, Katherine Pfister, Joanna Bons, Sivakama S Bharathi, Ayako Kinoshita, Bob B Zhang, Adam Richert, Birgit Schilling and 2 more

Abstract read
In one paragraph

Article in JCI insight, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Takuto ChibaDepartment of Pediatrics, University of Pittsburgh Medical Center Children's Hospital of Pittsburgh (UPMC CHP), University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Akira OdaDepartment of Pediatrics, University of Pittsburgh Medical Center Children's Hospital of Pittsburgh (UPMC CHP), University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Yuxun ZhangDepartment of Pediatrics, University of Pittsburgh Medical Center Children's Hospital of Pittsburgh (UPMC CHP), University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Katherine PfisterDepartment of Pediatrics, University of Pittsburgh Medical Center Children's Hospital of Pittsburgh (UPMC CHP), University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Joanna BonsBuck Institute for Research on Aging, Novato, California, USA.
Sivakama S BharathiDepartment of Pediatrics, University of Pittsburgh Medical Center Children's Hospital of Pittsburgh (UPMC CHP), University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Ayako KinoshitaDepartment of Pediatrics, University of Pittsburgh Medical Center Children's Hospital of Pittsburgh (UPMC CHP), University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Bob B ZhangDepartment of Pediatrics, University of Pittsburgh Medical Center Children's Hospital of Pittsburgh (UPMC CHP), University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Adam RichertDepartment of Pediatrics, University of Pittsburgh Medical Center Children's Hospital of Pittsburgh (UPMC CHP), University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Birgit SchillingBuck Institute for Research on Aging, Novato, California, USA.
Eric GoetzmanDepartment of Pediatrics, University of Pittsburgh Medical Center Children's Hospital of Pittsburgh (UPMC CHP), University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Sunder Sims-LucasDepartment of Pediatrics, University of Pittsburgh Medical Center Children's Hospital of Pittsburgh (UPMC CHP), University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Funding

The role of Sirtuin 5 in acute kidney injuryR01DK121758 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SIMS-LUCAS, SUNDER · 2020 to 2024
$2.3M
Dicarboxylic acid therapy for prevention of kidney injuryR01DK134346 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ERIC S GOETZMAN, Sunder Sims-Lucas · 2024 to 2026
$1.9M
Optimizing medium-chain lipids for the treatment of long-chain fatty acid oxidation disordersR01HD103602 · NICHD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GOETZMAN, ERIC S · 2021 to 2025
$1.7M
Orbitrap Fusion Lumos ETD with FAIMS ProS10OD028654 · OD · BUCK INSTITUTE FOR RESEARCH ON AGING · PI SCHILLING, BIRGIT · 2020 to 2020
$1.1M
The University of Pittsburgh Summer Research Internship Program kidney workshop (SRIP-Kid)R25DK119180 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JACQUELINE HO, Sunder Sims-Lucas · 2021 to 2026
$648k
TripleTOF 5600 High Resolution Mass SpectrometerS10OD016281 · OD · BUCK INSTITUTE FOR RESEARCH ON AGING · PI GIBSON, BRADFORD WAYNE · 2013 to 2013
$597k
The role of maladaptive VEGFR2 signaling in renal stroma for chronic kidney diseaseK01DK133635 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Takuto Greco Chiba · 2023 to 2026
$481k
The role of Sirtuin 5 in acute kidney injuryR56DK121758 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SIMS-LUCAS, SUNDER · 2019 to 2019
$94k
NICHD NIH HHS R01 HD103602NIDDK NIH HHS K01 DK133635NIDDK NIH HHS R01 DK121758NIDDK NIH HHS R01 DK134346NIDDK NIH HHS R25 DK119180NIDDK NIH HHS R56 DK121758NIH HHS S10 OD016281NIH HHS S10 OD028654
6 · The paper itself

Abstract

The renal tubular epithelial cells (RTECs) are particularly vulnerable to acute kidney injury (AKI). While fatty acids are the preferred energy source for RTECs via fatty acid oxidation (FAO), FAO-mediated H2O2 production in mitochondria has been shown to be a major source of oxidative stress. We have previously shown that a mitochondrial flavoprotein, long-chain acyl-CoA dehydrogenase (LCAD), which catalyzes a key step in mitochondrial FAO, directly produces H2O2 in vitro. Furthermore, we showed that renal LCAD becomes hyposuccinylated during AKI. Here, we demonstrated that succinylation of recombinant LCAD protein suppresses the production of H2O2. Following 2 distinct models of AKI, cisplatin treatment or renal ischemia/reperfusion injury (IRI), LCAD-/- mice demonstrated renoprotection. Specifically, LCAD-/- kidneys displayed mitigated renal tubular injury, decreased oxidative stress, preserved mitochondrial function, enhanced peroxisomal FAO, and decreased ferroptotic cell death. LCAD deficiency confers protection against 2 distinct models of AKI. This suggests a therapeutically attractive mechanism whereby preserved mitochondrial respiration as well as enhanced peroxisomal FAO by loss of LCAD mediates renoprotection against AKI.

Indexed as

Acute Kidney InjuryAcyl-CoA Dehydrogenase, Long-ChainAnimalsCisplatinDisease Models, AnimalEpithelial CellsFatty AcidsHumansHydrogen PeroxideKidney TubulesMaleMiceMice, Inbred C57BLMice, KnockoutMitochondriaOxidation-ReductionAcyl-CoA Dehydrogenase, Long-ChainCisplatinFatty AcidsHydrogen PeroxideCell stressFatty acid oxidationMetabolismNephrology

Identifiers

PMID39932791
PMCPMC11949023

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.