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December 1, 2023Life MetabolismOpen Access

Inhibiting fatty acid oxidation via Cpt1b knockout promotes adult heart regeneration by increasing α-ketoglutarate.

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Why the study?

Adult mammalian cardiomyocytes have limited proliferative capacity to compensate for cardiomyocyte loss, and the mechanisms by which metabolic changes control cycling genes to promote cardiac regeneration remained unknown.

Does inhibiting fatty acid oxidation via Cpt1b knockout promote cardiomyocyte proliferation and heart regeneration in preclinical models?

Population

Constitutive alphaMHC-Cre or tamoxifen-inducible alphaMHC-MerCreMer Cpt1b knockout mice and cultured neonatal cardiomyocytes

Comparison

Cpt1b knockout or metabolic/epigenetic manipulation vs controls

Design

Preclinical animal and cell-culture study

Key result

Inhibiting fatty acid oxidation via Cpt1b knockout promoted adult cardiomyocyte proliferation and heart regeneration by increasing α-ketoglutarate levels and altering epigenetic modifications.

Authors

XLXiuxiu LiuBZBin Zhou

Discussion

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Overview

Hypothesis-generating for metabolic modulation of cardiomyocyte proliferation; prospective trials needed before clinical consideration in heart failure.

Structured PICO

Does inhibiting fatty acid oxidation via Cpt1b knockout promote cardiomyocyte proliferation and heart regeneration in preclinical models?

P
Population
Preclinical models including Cpt1b knockout mice (constitutive αMHC-Cre or tamoxifen-inducible αMHC-MerCreMer lines) and cultured neonatal cardiomyocytes.
I
Intervention
Inhibition of fatty acid oxidation via Cpt1b knockout/knockdown, and manipulation of α-ketoglutarate (αKG) or KDM5 pathways.
C
Comparator
Control mouse hearts and control cultured cardiomyocytes.
O
Outcome
Cardiomyocyte proliferation, heart regeneration after ischemia-reperfusion injury, and epigenetic modifications (H3K4me3).surrogate

Inhibiting fatty acid oxidation via Cpt1b knockout promotes adult cardiomyocyte proliferation and heart regeneration by altering metabolic fluxes and epigenetic modifications, offering a potential therapeutic target for heart failure.

Limitations

  • Need to rule out secondary effects when targeting metabolic or epigenetic genes
  • Need for in vivo data on gene-specific overexpression in cardiomyocytes
  • Unclear whether regression to an immature state precedes or accompanies proliferation

Cite This Study

Liu et al. (2023) conducted an editorial in Heart failure. Cpt1b knockout vs. Control was evaluated on Cardiomyocyte proliferation. Inhibiting fatty acid oxidation via Cpt1b knockout promoted adult cardiomyocyte proliferation and heart regeneration by increasing α-ketoglutarate levels and altering epigenetic modifications.

synapsesocial.com/papers/6aa92a73d6d58a1cc10c03d7https://doi.org/10.1093/lifemeta/load047
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1DHA, a potentially therapeutic lipid for myocardial infarction2025
  2. 2Metabolic Reprogramming: A Byproduct or a Driver of Cardiomyocyte Proliferation?2024 · 83 citations
  3. 3Metabolic Determinants of Cardiomyocyte Proliferation2022 · 45 citations
  4. 4To proliferate or not to proliferate2010 · 7 citations
  5. 5Metabolic flux analyses to assess the differentiation of adult cardiac progenitors after fatty acid supplementation2019 · 21 citations