Evidence mapPaperPMID 38414784Full record

ArticleExperimental and therapeutic medicine2024

Lithium downregulates phosphorylated acetyl‑CoA carboxylase 2 and attenuates mitochondrial fatty acid utilization and oxidative stress in cardiomyocytes.

Pao-Huan Chen, Ting-Wei Lee, Shuen-Hsin Liu, Tin Van Huynh, Cheng-Chih Chung, Yung-Hsin Yeh, Yu-Hsun Kao, Yi-Jen Chen

Abstract read
In one paragraph

Article in Experimental and therapeutic medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Therapeutic Lithium Enhances Klotho Expression and Mitochondrial Size and Branching in Human Cardiac Fibroblasts Involving Nuclear Factor-kappa B Inhibition.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2026
    Article
  2. 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.

Pao-Huan ChenGraduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan, R.O.C.
Ting-Wei LeeDivision of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan, R.O.C.
Shuen-Hsin LiuGraduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan, R.O.C.
Tin Van HuynhInternational PhD Program in Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan, R.O.C.
Cheng-Chih ChungDivision of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan, R.O.C.
Yung-Hsin YehDivision of Cardiology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan, R.O.C.
Yu-Hsun KaoGraduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan, R.O.C.
Yi-Jen ChenGraduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan, R.O.C.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Acetyl-CoA carboxylase 2 plays a crucial role in regulating mitochondrial fatty acid oxidation in cardiomyocytes. Lithium, a monovalent cation known for its cardioprotective potential, has been investigated for its influence on mitochondrial bioenergetics. The present study explored whether lithium modulated acetyl-CoA carboxylase 2 and mitochondrial fatty acid metabolism in cardiomyocytes and the potential therapeutic applications of lithium in alleviating metabolic stress. Mitochondrial bioenergetic function, fatty acid oxidation, reactive oxygen species production, membrane potential and the expression of proteins involved in fatty acid metabolism in H9c2 cardiomyocytes treated with LiCl for 48 h was measured by using a Seahorse extracellular flux analyzer, fluorescence microscopy and western blotting. Small interfering RNA against glucose transporter type 4 was transfected into H9c2 cardiomyocytes for 48 h to induce metabolic stress mimicking insulin resistance. The results revealed that LiCl at a concentration of 0.3 mM (but not at a concentration of 0.1 or 1.0 mM) upregulated the expression of phosphorylated (p-)glycogen synthase kinase-3 beta and downregulated the expression of p-acetyl-CoA carboxylase 2 but did not affect the expression of adenosine monophosphate-activated protein kinase or calcineurin. Cotreatment with TWS119 (8 µM) and LiCl (0.3 mM) downregulated p-acetyl-CoA carboxylase 2 expression to a similar extent as did treatment with TWS119 (8 µM) alone. Moreover, LiCl (0.3 mM) inhibited mitochondrial fatty acid oxidation, improved coupling efficiency and the cellular respiratory control ratio, hindered reactive oxygen species production and proton leakage and restored mitochondrial membrane potential in glucose transporter type 4 knockdown-H9c2 cardiomyocytes. These findings suggested that low therapeutic levels of lithium can downregulate p-acetyl-CoA carboxylase 2, thus reducing mitochondrial fatty acid oxidation and oxidative stress in cardiomyocytes.

Indexed as

acetyl-CoA carboxylasecardiac metabolismcardioprotectionfatty acid oxidationglycogen synthase kinase-3 betalithiumreactive oxygen species

Identifiers

PMID38414784
PMCPMC10895620

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.