Evidence map›Paper›PMID 33989657›Full record

ArticleJournal of molecular and cellular cardiology2021

Increasing fatty acid oxidation elicits a sex-dependent response in failing mouse hearts.

Julia Ritterhoff, Timothy S McMillen, Outi Villet, Sara Young, Stephen C Kolwicz, Taurence Senn, Arianne Caudal, Rong Tian

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

Article in Journal of molecular and cellular cardiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
4.2field-weighted citation impact, top 5% 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

25 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Metabolic Reprogramming in Heart Failure: From Energy Starvation to Therapeutic Targets.Current treatment options in cardiovascular medicine · 2025
    Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Observational
  13. Peripheral Blood Cells From Older Adults Exhibit Sex-Associated Differences in Mitochondrial Function.The journals of gerontology. Series A, Biological sciences and medical sciences · 2024
    Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Application of 4-D ultrasound-derived regional strain and proteomics analysis inAmerican journal of physiology. Heart and circulatory physiology · 2023
    Article
  19. Review
  20. Review
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

8 authors at 1 institution in 1 country.

Julia RitterhoffMitochondria and Metabolism Center, Department of Anesthesiology and Pain Medicine, University of Washington, Republican Street 850, 98109 Seattle, WA, USA.
Timothy S McMillenMitochondria and Metabolism Center, Department of Anesthesiology and Pain Medicine, University of Washington, Republican Street 850, 98109 Seattle, WA, USA.
Outi VilletMitochondria and Metabolism Center, Department of Anesthesiology and Pain Medicine, University of Washington, Republican Street 850, 98109 Seattle, WA, USA.
Sara YoungMitochondria and Metabolism Center, Department of Anesthesiology and Pain Medicine, University of Washington, Republican Street 850, 98109 Seattle, WA, USA.
Stephen C KolwiczMitochondria and Metabolism Center, Department of Anesthesiology and Pain Medicine, University of Washington, Republican Street 850, 98109 Seattle, WA, USA; Heart and Muscle Metabolism Laboratory, Health and Exercise Physiology, Ursinus College, Collegeville, PA 19426, USA.
Taurence SennDepartment of Medicinal Chemistry, School of Pharmacy, University of Washington, H172 Health Science Building, 98195 Seattle, WA, USA.
Arianne CaudalMitochondria and Metabolism Center, Department of Anesthesiology and Pain Medicine, University of Washington, Republican Street 850, 98109 Seattle, WA, USA.
Rong TianMitochondria and Metabolism Center, Department of Anesthesiology and Pain Medicine, University of Washington, Republican Street 850, 98109 Seattle, WA, USA. Electronic address: rongtian@u.washington.edu.
University of Washington · US

Funding

NAD+/NADH ratio, protein acetylation and mitochondrial functionR01HL110349 · NHLBI · UNIVERSITY OF WASHINGTON · PI TIAN, RONG · 2011 to 2020
$5.7M
Fatty acid oxidation suppresses cardiac hypertrophyR01HL129510 · NHLBI · UNIVERSITY OF WASHINGTON · PI TIAN, RONG · 2015 to 2018
$2.8M
Mitochondrial function and glycolytic switch in pathological cardiac hypertrophyR01HL142628 · NHLBI · UNIVERSITY OF WASHINGTON · PI TIAN, RONG · 2018 to 2021
$2.4M
Bruker Avance III 600 MHz (14T) Wide Bore SpectrometerS10RR029021 · NCRR · UNIVERSITY OF WASHINGTON · PI KUSHMERICK, MARTIN J · 2010 to 2010
$1.0M
American Heart Association-American Stroke Association 14SDG18590020NCRR NIH HHS S10 RR029021NHLBI NIH HHS R01 HL110349NHLBI NIH HHS R01 HL129510NHLBI NIH HHS R01 HL142628
6 · The paper itself

Abstract

backgroundReduced fatty acid oxidation (FAO) is a hallmark of metabolic remodeling in heart failure. Enhancing mitochondrial long-chain fatty acid uptake by Acetyl-CoA carboxylase 2 (ACC2) deletion increases FAO and prevents cardiac dysfunction during chronic stresses, but therapeutic efficacy of this approach has not been determined.

methodsMale and female ACC2 f/f-MCM (ACC2KO) and their respective littermate controls were subjected to chronic pressure overload by TAC surgery. Tamoxifen injection 3 weeks after TAC induced ACC2 deletion and increased FAO in ACC2KO mice with pathological hypertrophy.

resultsACC2 deletion in mice with pre-existing cardiac pathology promoted FAO in female and male hearts, but improved cardiac function only in female mice. In males, pressure overload caused a downregulation in the mitochondrial oxidative function. Stimulating FAO by ACC2 deletion caused unproductive acyl-carnitine accumulation, which failed to improve cardiac energetics. In contrast, mitochondrial oxidative capacity was sustained in female pressure overloaded hearts and ACC2 deletion improved myocardial energetics. Mechanistically, we revealed a sex-dependent regulation of PPARα signaling pathway in heart failure, which accounted for the differential response to ACC2 deletion.

conclusionMetabolic remodeling in the failing heart is sex-dependent which could determine the response to metabolic intervention. The findings suggest that both mitochondrial oxidative capacity and substrate preference should be considered for metabolic therapy of heart failure.

Indexed as

Acetyl-CoA CarboxylaseAnimalsCarnitineDisease Models, AnimalEnergy MetabolismFatty AcidsFemaleGene DeletionHeart FailureMaleMiceMice, Inbred C57BLMice, TransgenicMyocardiumOxidation-ReductionPPAR alphaAcacb protein, mouseAcetyl-CoA CarboxylaseacylcarnitineCarnitineFatty AcidsPPAR alphaPpara protein, mouseTamoxifenEnergy metabolismFatty acid oxidationHeart failure

Identifiers

PMID33989657
PMCPMC8405556
OpenAlexW3160468512

What OpenQuestion holds

Textmetadata
LicenceTDM
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.