Evidence map›Paper›PMID 31166588›Full record

ArticleCardiovascular research2020

Low cardiac lipolysis reduces mitochondrial fission and prevents lipotoxic heart dysfunction in Perilipin 5 mutant mice.

Stephanie Kolleritsch, Benedikt Kien, Gabriele Schoiswohl, Clemens Diwoky, Renate Schreiber, Christoph Heier, Lisa Katharina Maresch, Martina Schweiger, Thomas O Eichmann, Sarah Stryeck and 10 more

Erratum issuedOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cardiovascular research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
3.4field-weighted citation impact, top 8% 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

41 citing papers in PubMed, 50 citations in OpenAlex.

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  4. ALCAT1 promotes diabetic cardiomyopathy by linking myocardial tetralinoleoyl cardiolipin deficiency to lipotoxicity.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 3 institutions in 1 country.

Stephanie KolleritschInstitute of Molecular Biosciences, University of Graz, Heinrichstrasse 31, 8010 Graz, Austria.
Benedikt KienInstitute of Molecular Biosciences, University of Graz, Heinrichstrasse 31, 8010 Graz, Austria.
Gabriele SchoiswohlInstitute of Molecular Biosciences, University of Graz, Heinrichstrasse 31, 8010 Graz, Austria.
Clemens DiwokyInstitute of Molecular Biosciences, University of Graz, Heinrichstrasse 31, 8010 Graz, Austria.
Renate SchreiberInstitute of Molecular Biosciences, University of Graz, Heinrichstrasse 31, 8010 Graz, Austria.
Christoph HeierInstitute of Molecular Biosciences, University of Graz, Heinrichstrasse 31, 8010 Graz, Austria.
Lisa Katharina MareschInstitute of Molecular Biosciences, University of Graz, Heinrichstrasse 31, 8010 Graz, Austria.
Martina SchweigerInstitute of Molecular Biosciences, University of Graz, Heinrichstrasse 31, 8010 Graz, Austria.
Thomas O EichmannInstitute of Molecular Biosciences, University of Graz, Heinrichstrasse 31, 8010 Graz, Austria.
Sarah StryeckInstitute of Molecular Biology and Biochemistry, Medical University of Graz, 8010 Graz, Austria.
Petra KrennOmics Center Graz, BioTechMed-Graz, 8010 Graz, Austria.
Tamara TominOmics Center Graz, BioTechMed-Graz, 8010 Graz, Austria.
Matthias SchittmayerOmics Center Graz, BioTechMed-Graz, 8010 Graz, Austria.
Dagmar KolbInstitute of Cell Biology, Histology and Embryology, Medical University of Graz, 8010 Graz, Austria.
Thomas RülickeInstitute of Laboratory Animal Science, University of Veterinary Medicine Vienna, 1210 Vienna, Austria.
Gerald HoeflerDiagnostic & Research Institute of Pathology, Medical University of Graz, 8010 Graz, Austria.
Heimo WolinskiInstitute of Molecular Biosciences, University of Graz, Heinrichstrasse 31, 8010 Graz, Austria.
Tobias MadlInstitute of Molecular Biology and Biochemistry, Medical University of Graz, 8010 Graz, Austria.
Ruth Birner-GruenbergerOmics Center Graz, BioTechMed-Graz, 8010 Graz, Austria.
Guenter HaemmerleInstitute of Molecular Biosciences, University of Graz, Heinrichstrasse 31, 8010 Graz, Austria.
University of Graz · ATMedical University of Graz · ATUniversity of Veterinary Medicine Vienna · AT

Funding

Austrian Science Fund FWF F 3001Austrian Science Fund FWF P 28882Austrian Science Fund FWF P 29253Austrian Science Fund FWF W 1226
6 · The paper itself

Abstract

aimsLipotoxic cardiomyopathy in diabetic and obese patients typically encompasses increased cardiac fatty acid (FA) uptake eventually surpassing the mitochondrial oxidative capacity. Lowering FA utilization via inhibition of lipolysis represents a strategy to counteract the development of lipotoxic heart dysfunction. However, defective cardiac triacylglycerol (TAG) catabolism and FA oxidation in humans (and mice) carrying mutated ATGL alleles provokes lipotoxic heart dysfunction questioning a therapeutic approach to decrease cardiac lipolysis. Interestingly, decreased lipolysis via cardiac overexpression of Perilipin 5 (Plin5), a binding partner of ATGL, is compatible with normal heart function and lifespan despite massive cardiac lipid accumulation. Herein, we decipher mechanisms that protect Plin5 transgenic mice from the development of heart dysfunction. METHODS AND

resultsWe generated mice with cardiac-specific overexpression of Plin5 encoding a serine-155 to alanine exchange (Plin5-S155A) of the protein kinase A phosphorylation site, which has been suggested as a prerequisite to stimulate lipolysis and may play a crucial role in the preservation of heart function. Plin5-S155A mice showed a substantial increase in cardiac TAG and ceramide levels, which was comparable to mice overexpressing non-mutated Plin5. Lipid accumulation was compatible with normal heart function even under mild stress. Plin5-S155A mice showed reduced cardiac FA oxidation but normal ATP production and changes in the Plin5-S155A phosphoproteome compared to Plin5 transgenic mice. Interestingly, mitochondrial recruitment of dynamin-related protein 1 (Drp1) was markedly reduced in cardiac muscle of Plin5-S155A and Plin5 transgenic mice accompanied by decreased phosphorylation of mitochondrial fission factor, a mitochondrial receptor of Drp1.

conclusionsThis study suggests that low cardiac lipolysis is associated with reduced mitochondrial fission and may represent a strategy to combat the development of lipotoxic heart dysfunction.

Indexed as

LipolysisMitochondrial DynamicsAdenosine TriphosphateAdipose TissueAnimalsCeramidesChlorocebus aethiopsCOS CellsDisease Models, AnimalDynaminsFatty AcidsHeart DiseasesIntracellular Signaling Peptides and ProteinsMembrane ProteinsMice, Mutant StrainsMitochondria, HeartAdenosine TriphosphateCeramidesDnm1l protein, mouseDynaminsFatty AcidsIntracellular Signaling Peptides and Proteinslipid storage droplet protein 5, mouseMembrane Proteinsmitochondrial fission factor, mouseMitochondrial ProteinsMuscle ProteinsTriglyceridesCardiac lipolysisHeart dysfunctionLipotoxicityMitochondrial dynamicsPerilipin 5

Identifiers

PMID31166588
PMCPMC7338219
OpenAlexW2944307659

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.