Evidence map›Paper›PMID 25713290›Full record

ArticleJournal of the American Heart Association2015

Cardiac energy dependence on glucose increases metabolites related to glutathione and activates metabolic genes controlled by mechanistic target of rapamycin.

Jonathan C Schisler, Trisha J Grevengoed, Florencia Pascual, Daniel E Cooper, Jessica M Ellis, David S Paul, Monte S Willis, Cam Patterson, Wei Jia, Rosalind A Coleman

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

Article in Journal of the American Heart Association, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

26 citing papers in PubMed, 37 citations in OpenAlex.

  1. Review
  2. Article
  3. Tissue specific roles of fatty acid oxidation.Advances in biological regulation · 2025
    Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Modeling the Transition From Decompensated to Pathological Hypertrophy.Journal of the American Heart Association · 2018
    Article
  18. Review
  19. Article
  20. 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

10 authors at 1 institution in 1 country.

Jonathan C SchislerDivision of Cardiology, Department of Medicine, University of North Carolina, Chapel Hill, NC (J.C.S., C.P.).
Trisha J GrevengoedDepartment of Nutrition, University of North Carolina, Chapel Hill, NC (T.J.G., F.P., D.E.C., J.M.E., D.S.P., R.A.C.).
Florencia PascualDepartment of Nutrition, University of North Carolina, Chapel Hill, NC (T.J.G., F.P., D.E.C., J.M.E., D.S.P., R.A.C.).
Daniel E CooperDepartment of Nutrition, University of North Carolina, Chapel Hill, NC (T.J.G., F.P., D.E.C., J.M.E., D.S.P., R.A.C.).
Jessica M EllisDepartment of Nutrition, University of North Carolina, Chapel Hill, NC (T.J.G., F.P., D.E.C., J.M.E., D.S.P., R.A.C.).
David S PaulDepartment of Nutrition, University of North Carolina, Chapel Hill, NC (T.J.G., F.P., D.E.C., J.M.E., D.S.P., R.A.C.).
Monte S WillisDepartment of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC (M.S.W.).
Cam PattersonDivision of Cardiology, Department of Medicine, University of North Carolina, Chapel Hill, NC (J.C.S., C.P.).
Wei JiaNutrition Research Institute, Kannapolis, NC (W.J.).
Rosalind A ColemanDepartment of Nutrition, University of North Carolina, Chapel Hill, NC (T.J.G., F.P., D.E.C., J.M.E., D.S.P., R.A.C.).
University of North Carolina at Chapel Hill · US

Funding

UNIV OF NORTH CAROLINA CLINICAL NUTRITION RESEARCH UNITP30DK056350 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Ian Michael Carroll · 1999 to 2026
$31.6M
Pre-doctoral Training Program in Integrative Vascular BiologyT32HL069768 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Christopher P. Mack · 2002 to 2026
$9.7M
Acyl-CoA Synthetase: Structure, Function and RegulationR01DK059935 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI COLEMAN, ROSALIND ANNE · 2002 to 2015
$4.7M
Myocyte Signaling and the Response to StressR37HL065619 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI PATTERSON, WINSTON C · 2010 to 2019
$3.7M
CHIP: A link between the chaperone &proteasome systemsR01GM061728 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SCHISLER, JONATHAN C. · 2001 to 2013
$3.4M
Myocyte specific regulation of metabolism and the response to biomechanical forceR01HL104129 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI WILLIS, MONTE S · 2010 to 2018
$3.3M
NHLBI NIH HHS 5R37HL065619NHLBI NIH HHS HL104129NHLBI NIH HHS R01 HL104129NHLBI NIH HHS R37 HL065619NHLBI NIH HHS T32 HL069768NHLBI NIH HHS T32HL069768NIDDK NIH HHS DK056350NIDDK NIH HHS DK59935NIDDK NIH HHS P30 DK056350NIDDK NIH HHS R01 DK059935NIGMS NIH HHS 5R01GM-061728NIGMS NIH HHS R01 GM061728
6 · The paper itself

Abstract

backgroundLong chain acyl-CoA synthetases (ACSL) catalyze long-chain fatty acids (FA) conversion to acyl-CoAs. Temporal ACSL1 inactivation in mouse hearts (Acsl1(H-/-)) impaired FA oxidation and dramatically increased glucose uptake, glucose oxidation, and mTOR activation, resulting in cardiac hypertrophy. We used unbiased metabolomics and gene expression analyses to elucidate the cardiac cellular response to increased glucose use in a genetic model of inactivated FA oxidation. METHODS AND

resultsMetabolomics analysis identified 60 metabolites altered in Acsl1(H-/-) hearts, including 6 related to glucose metabolism and 11 to cysteine and glutathione pathways. Concurrently, global cardiac transcriptional analysis revealed differential expression of 568 genes in Acsl1(H-/-) hearts, a subset of which we hypothesized were targets of mTOR; subsequently, we measured the transcriptional response of several genes after chronic mTOR inhibition via rapamycin treatment during the period in which cardiac hypertrophy develops. Hearts from Acsl1(H-/-) mice increased expression of several Hif1α-responsive glycolytic genes regulated by mTOR; additionally, expression of Scl7a5, Gsta1/2, Gdf15, and amino acid-responsive genes, Fgf21, Asns, Trib3, Mthfd2, were strikingly increased by mTOR activation.

conclusionsThe switch from FA to glucose use causes mTOR-dependent alterations in cardiac metabolism. We identified cardiac mTOR-regulated genes not previously identified in other cellular models, suggesting heart-specific mTOR signaling. Increased glucose use also changed glutathione-related pathways and compensation by mTOR. The hypertrophy, oxidative stress, and metabolic changes that occur within the heart when glucose supplants FA as a major energy source suggest that substrate switching to glucose is not entirely benign.

Indexed as

AnimalsCarbohydrate MetabolismCoenzyme A LigasesCysteineFatty AcidsGlucoseGlutathioneLipid MetabolismMiceMice, KnockoutMyocardiumOxidation-ReductionSirolimusTOR Serine-Threonine KinasesACSL1 protein, mouseCoenzyme A LigasesCysteineFatty AcidsGlucoseGlutathioneMTOR protein, humanSirolimusTOR Serine-Threonine Kinasesacyl‐CoA synthetasefuel switchingglutathionemTORoxidative stress

Identifiers

PMID25713290
PMCPMC4345858
OpenAlexW2126181836

What OpenQuestion holds

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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.