Evidence map›Paper›PMID 40164334›Full record

ArticleJournal of lipid research2025

Cardiomyopathy in a c.1528G>C Hadha mouse is associated with cardiac tissue lipotoxicity and altered cardiolipin species.

Chibuike Eke, Shannon Babcock, Garen Gaston, Gabriela Elizondo, Hak Chung, Ayah Asal, Kathryn C Chatfield, Genevieve C Sparagna, Andrea E DeBarber, William Packwood and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of lipid research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Acute arrhythmias in a long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency mouse model.American journal of physiology. Heart and circulatory physiology · 2026
    Article
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

12 authors.

Chibuike EkeDepartment of Molecular and Medical Genetics, Oregon Health and Science University, Portland, Oregon, USA.
Shannon BabcockDepartment of Molecular and Medical Genetics, Oregon Health and Science University, Portland, Oregon, USA.
Garen GastonDepartment of Molecular and Medical Genetics, Oregon Health and Science University, Portland, Oregon, USA.
Gabriela ElizondoDepartment of Molecular and Medical Genetics, Oregon Health and Science University, Portland, Oregon, USA.
Hak ChungDepartment of Molecular and Medical Genetics, Oregon Health and Science University, Portland, Oregon, USA.
Ayah AsalDepartment of Molecular and Medical Genetics, Oregon Health and Science University, Portland, Oregon, USA.
Kathryn C ChatfieldDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Children's Hospital Colorado, Aurora, Colorado, USA; Division of Cardiology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Genevieve C SparagnaDivision of Cardiology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Andrea E DeBarberDepartment of Chemical Physiology & Biochemistry, Oregon Health and Science University, Portland, Oregon, USA.
William PackwoodDepartment of Chemical Physiology & Biochemistry, Oregon Health and Science University, Portland, Oregon, USA.
Jonathan R LindnerKnight Cardiovascular Institute, Oregon Health and Science University, Portland, Oregon, USA; Cardiovascular Division, The University of Virginia Medical Center, Charlottesville, Virginia, USA.
Melanie B GillinghamDepartment of Molecular and Medical Genetics, Oregon Health and Science University, Portland, Oregon, USA. Electronic address: gillingm@ohsu.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) is a metabolic disorder caused by the loss of LCHAD enzymatic activity in the α-subunit of the trifunctional protein (TFPα), leading to impaired fatty acid oxidation (FAO). Patients with LCHADD often develop dilated cardiomyopathy. A previously unrecognized enzymatic function of TFPα as monolysocardiolipin acyltransferase (MLCL-AT) has been implicated in cardiolipin remodeling, crucial for mitochondrial cristae integrity. However, it remains unclear whether the common pathogenic variant c.1528G>C in HADHA impairs MLCL-AT activity in TFPα. In this study, we investigated whether cardiac cardiolipin profiles are altered in LCHADD and explored potential pathophysiological mechanisms, including heart lipid accumulation, changes in the cardiolipin synthesis pathway, and mitochondrial dynamics, utilizing a murine model of LCHADD carrying c.1528G>C variant that mimics the cardiomyopathy observed in humans. LCHADD mice developed eccentric hypertrophic cardiomyopathy from 3- to 12 months of age. 12-month-old LCHADD hearts exhibited altered cardiolipin profiles and increased oxidized cardiolipin. LCHADD hearts had higher lipid content, and the shift in fatty acid profile mirrored the shift in cardiolipin profile compared to wild-type controls, suggesting altered cardiolipin composition in LCHADD may be a reflection of accumulated lipids caused by lower FAO. No differential expression of cardiolipin synthesis and remodeling pathway enzymes was observed, suggesting minimal impact of the c.1528G>C variant on cardiolipin remodeling pathway. LCHADD hearts showed an altered ratio of OPA1 isoforms, and mitochondria with swelling and disorganized cristae were present. These findings suggest that altered fatty acid, cardiolipin profiles, and mitochondrial dynamics may contribute to LCHADD cardiomyopathy, warranting further studies.

Indexed as

CardiolipinsCardiomyopathiesLipid Metabolism, Inborn ErrorsLong-Chain-3-Hydroxyacyl-CoA DehydrogenaseMitochondrial Trifunctional ProteinMitochondrial Trifunctional Protein, alpha SubunitMyocardiumPurpuraAcyltransferasesAnimalsDisease Models, AnimalFatty AcidsHumansMaleMiceMitochondrial MyopathiesAcyltransferasesCardiolipinsFatty AcidsLong-Chain-3-Hydroxyacyl-CoA DehydrogenaseMitochondrial Trifunctional ProteinMitochondrial Trifunctional Protein, alpha Subunitcardiolipinfatty acid oxidationlipid dropletsLipids/oxidationlipolysis and fatty acid metabolismmitochondriaoxidized lipidsphospholipids

Identifiers

PMID40164334
PMCPMC12084506

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.