Evidence map›Paper›PMID 39524205›Full record

ArticleJHEP reports : innovation in hepatology2024

Palmitoylcarnitine impairs immunity in decompensated cirrhosis.

Ingrid Wei Zhang, María Belén Sánchez-Rodríguez, Cristina López-Vicario, Mireia Casulleras, Marta Duran-Güell, Roger Flores-Costa, Ferran Aguilar, Michael Rothe, Paula Segalés, Carmen García-Ruiz and 4 more

Abstract read
In one paragraph

Article in JHEP reports : innovation in hepatology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

  1. Review
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  9. Observational
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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

14 authors.

Ingrid Wei ZhangBiochemistry and Molecular Genetics Service, Hospital Clínic, IDIBAPS, Barcelona, Spain.
María Belén Sánchez-RodríguezBiochemistry and Molecular Genetics Service, Hospital Clínic, IDIBAPS, Barcelona, Spain.
Cristina López-VicarioBiochemistry and Molecular Genetics Service, Hospital Clínic, IDIBAPS, Barcelona, Spain.
Mireia CasullerasBiochemistry and Molecular Genetics Service, Hospital Clínic, IDIBAPS, Barcelona, Spain.
Marta Duran-GüellBiochemistry and Molecular Genetics Service, Hospital Clínic, IDIBAPS, Barcelona, Spain.
Roger Flores-CostaBiochemistry and Molecular Genetics Service, Hospital Clínic, IDIBAPS, Barcelona, Spain.
Ferran AguilarEuropean Foundation for the Study of Chronic Liver Failure (EF CLIF) and Grifols Chair, Barcelona, Spain.
Michael RotheLipidomix, Berlin, Germany.
Paula SegalésBiomedical Research Network on Hepatic and Digestive Diseases (CIBERehd), Spain.
Carmen García-RuizBiomedical Research Network on Hepatic and Digestive Diseases (CIBERehd), Spain.
José C Fernández-ChecaBiomedical Research Network on Hepatic and Digestive Diseases (CIBERehd), Spain.
Jonel TrebickaEuropean Foundation for the Study of Chronic Liver Failure (EF CLIF) and Grifols Chair, Barcelona, Spain.
Vicente ArroyoEuropean Foundation for the Study of Chronic Liver Failure (EF CLIF) and Grifols Chair, Barcelona, Spain.
Joan ClàriaBiochemistry and Molecular Genetics Service, Hospital Clínic, IDIBAPS, Barcelona, Spain.

Funding

The Southernearch Center for ALPD and CirrhosisP50AA011999 · NIAAA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ANNA S. GUKOVSKAYA · 1999 to 2026
$45.8M
NIAAA NIH HHS P50 AA011999
6 · The paper itself

Abstract

Background & Aims: In patients with cirrhosis, acute decompensation (AD) correlates with a hyperinflammatory state driven by mitochondrial dysfunction, which is a significant factor in the progression toward acute-on-chronic liver failure (ACLF). Elevated circulating levels of acylcarnitine, indicative of mitochondrial dysfunction, are predictors of mortality in ACLF patients. Our hypothesis posits that acylcarnitines not only act as biomarkers, but also actively exert detrimental effects on circulating immune cells. Methods: Plasma acylcarnitine levels were measured in 20 patients with AD cirrhosis and 10 healthy individuals. The effects of selected medium- and long-chain acylcarnitines on mitochondrial function were investigated in peripheral leucocytes from healthy donors by determining mitochondrial membrane potential (Δψm) and mitochondrial respiration using the JC-1 dye and Agilent Seahorse XF technology. Changes regarding mitochondrial ultrastructure and redox systems were assessed by transmission electron microscopy and gene and protein expression analysis. Results: Plasma levels of several acylcarnitine species were significantly elevated in patients with AD cirrhosis compared with healthy individuals, alongside increased levels of inflammatory mediators (cytokines and chemokines). Notably, the long-chain acylcarnitine palmitoylcarnitine (C16:0-carnitine, 1.51-fold higher, Conclusions: Our findings suggest that long-chain acylcarnitines induce mitochondrial injury in immune cells, thereby contributing to the development of immune dysfunction associated with cirrhosis. Impact and implications: Patients with acute decompensation of cirrhosis and acute-on-chronic liver failure (ACLF) display a systemic hyperinflammatory state and leukocyte mitochondrial dysfunction. We discovered that apart from being increased in the circulation of these patients, the long-chain palmitoylcarnitine is able to elicit cytokine secretion paired with mitochondrial dysfunction in leukocytes from healthy donors. In particular, we show that inhibiting the metabolism of palmitoylcarnitine could reverse these detrimental effects. Our findings underline the importance of immunometabolism as a treatment target in patients with acute decompensation of cirrhosis and ACLF.

Indexed as

Acute decompensation of cirrhosisAcylcarnitinesImmune cellsMitochondrial dysfunction

Identifiers

PMID39524205
PMCPMC11544064

What OpenQuestion holds

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Registered trials

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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.