Evidence map›Paper›PMID 37564204›Full record

ArticleInternational journal of biological sciences2023

Melatonin Ameliorates Hepatic Ferroptosis in NAFLD by Inhibiting ER Stress via the MT2/cAMP/PKA/IRE1 Signaling Pathway.

Qingyun Guan, Zixu Wang, Keyu Hu, Jing Cao, Yulan Dong, Yaoxing Chen

Open access · goldAbstract read
In one paragraph

Article in International journal of biological sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed, 2 pooled it
17.4field-weighted citation impact, top 1% 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

59 citing papers in PubMed, 2 syntheses or guidelines pooled it, 81 citations in OpenAlex.

  1. Pooled it
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  5. [The role of hepatocyte programmed cell death in liver fibrosis].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026
    Review
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  19. Molecular medicine reports · 2026
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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

6 authors at 1 institution in 1 country.

Qingyun GuanCollege of Veterinary Medicine, China Agricultural University, Haidian, Beijing 100193, China.
Zixu WangCollege of Veterinary Medicine, China Agricultural University, Haidian, Beijing 100193, China.
Keyu HuCollege of Veterinary Medicine, China Agricultural University, Haidian, Beijing 100193, China.
Jing CaoCollege of Veterinary Medicine, China Agricultural University, Haidian, Beijing 100193, China.
Yulan DongCollege of Veterinary Medicine, China Agricultural University, Haidian, Beijing 100193, China.
Yaoxing ChenCollege of Veterinary Medicine, China Agricultural University, Haidian, Beijing 100193, China.
China Agricultural University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Ferroptosis, an iron-dependent cell death form, has recently been observed in the development of non-alcoholic fatty liver disease (NAFLD). Melatonin (Mel) shows potential benefits for preventing and treating liver diseases. Whether and how Mel ameliorates hepatic ferroptosis in NAFLD is not fully understood. Here we established a mouse model of NAFLD induced by long-term high-fat diet (HFD) feeding. We found that Mel treatment ameliorated global metabolic abnormalities and inhibited the progression of NAFLD in mice. Most importantly, Mel supplementation significantly improved HFD-induced iron homeostasis disorders in the liver, including iron overload and ferritin transport disorders. For another, Mel ameliorated HFD-induced hepatic lipid peroxidation. The recuperative role of exogenous Mel on hepatocyte ferroptosis was also observed in PA- or Erastin-treated HepG2 cells. Mechanistically, MT2, but not MT1, was involved in the effect of Mel. Furthermore, Mel treatment inhibited HFD or Erastin-activated ER stress and activated the PKA/IRE1 signaling pathway. Co-expression of p-PKA and p-IRE1 was enhanced by the MT2 antagonist. Inhibitions of PKA and IRE1 respectively improved hepatocyte ferroptosis, and activations of cAMP/PKA reversed Mel's effect on ferroptosis. Collectively, these findings suggest that exogenous Mel inhibits hepatic ferroptosis in NAFLD by ameliorating ER stress through the MT2/cAMP/PKA/IRE1 pathway, proving that Mel is a promising candidate drug for the treatment of hepatic ferroptosis in NAFLD.

Indexed as

FerroptosisMelatoninNon-alcoholic Fatty Liver DiseaseAnimalsDiet, High-FatEndoplasmic Reticulum StressLiverMiceMice, Inbred C57BLProtein Serine-Threonine KinasesSignal TransductionMelatoninProtein Serine-Threonine KinasesER stressFerroptosisIRE1LiverMelatoninMT2NAFLD

Identifiers

PMID37564204
PMCPMC10411470
OpenAlexW4385711729

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.