Evidence map›Paper›PMID 42801580›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

A Hepatocyte-to-Stellate Cell Axis Couples Alternate-Day Fasting to Liver Fibrosis Resolution via ATG7 S-Nitrosylation.

Xueqiang Wang, Mengqi Zeng, Cunxiao Sun, Yuhan Gou, Zhaode Feng, Weiqiang Lv, Chaoying Yan, Hansen Wu, Pengfei Zhang, Jie Xu and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

18 authors.

Xueqiang Wang *Department of Geriatrics Cardiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.ORCID https://orcid.org/0000-0001-7476-401X
Mengqi Zeng *Shandong Engineering Research Center of Precision Intervention for Aging, Shandong Key Laboratory of Neurorehabilitation, School of Life Sciences and Health, University of Health and Rehabilitation Sciences, Qingdao, China.
Cunxiao SunFrontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China.
Yuhan GouFrontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China.
Zhaode FengCenter For Mitochondrial Biology and Medicine, School of Life Science and Technology, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Xi'an Jiaotong University, Xi'an, China.
Weiqiang LvFrontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China.
Chaoying YanDepartment of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Hansen WuFrontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China.
Pengfei ZhangKey Laboratory of Aerospace Medicine, School of Aerospace Medicine, Ministry of Education, Fourth Military Medical University, Xi'an, China.
Jie XuCenter For Mitochondrial Biology and Medicine, School of Life Science and Technology, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Xi'an Jiaotong University, Xi'an, China.
Ke CaoCenter For Mitochondrial Biology and Medicine, School of Life Science and Technology, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Xi'an Jiaotong University, Xi'an, China.
Hao LiCenter For Mitochondrial Biology and Medicine, School of Life Science and Technology, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Xi'an Jiaotong University, Xi'an, China.ORCID https://orcid.org/0000-0001-5677-3377
Mingge DingDepartment of Geriatrics Cardiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.ORCID https://orcid.org/0000-0001-9121-5151
Zhongbo LiuKey Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, China.ORCID https://orcid.org/0000-0003-0075-1261
Xing ZhangKey Laboratory of Aerospace Medicine, School of Aerospace Medicine, Ministry of Education, Fourth Military Medical University, Xi'an, China.ORCID https://orcid.org/0000-0001-6615-5038
Jiankang LiuShandong Engineering Research Center of Precision Intervention for Aging, Shandong Key Laboratory of Neurorehabilitation, School of Life Sciences and Health, University of Health and Rehabilitation Sciences, Qingdao, China.
Xuan ZouDepartment of Geriatrics Cardiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Zhihui FengDepartment of Geriatrics Cardiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.ORCID https://orcid.org/0000-0002-2448-6565

Funding

National Natural Science Foundation of China 32271184National Natural Science Foundation of China 32300654National Natural Science Foundation of China 32300976National Natural Science Foundation of China 32350025National Natural Science Foundation of China 32571330National Natural Science Foundation of China 82100918National Natural Science Foundation of China 82271727National Natural Science Foundation of China 82300902National Natural Science Foundation of China 82300951Natural Science Basic Research Plan in Shaanxi Province 2025JC-QYCX-018Noncommunicable Chronic Diseases-National Science and Technology Major Project 2025ZD0549700Opening Research Fund from Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University 2023LHM-KFKT001Shandong Provincial Natural Foundation ZR2023JQ011
6 · The paper itself

Abstract

Communication between hepatocytes and hepatic stellate cells (HSCs) is essential for liver homeostasis, yet its potential role in mitigating fibrosis remains largely unexplored. Here, we define a protective signaling axis from hepatocytes to HSCs, mediated by hepatocyte-expressed eNOS, that restrains HSC activation and fibrotic progression. In human fibrotic liver samples and mouse models, eNOS expression is markedly suppressed, and its hepatocyte-specific deletion aggravates injury and fibrosis. We further establish that the anti-fibrotic benefits of alternate-day fasting (ADF) critically depend on this intercellular pathway. ADF enhanced hepatocyte eNOS expression, and hepatocyte-specific eNOS knockout abolished the protective metabolic and anti-fibrotic effects of ADF. Mechanistically, ADF downregulates the mitochondrial chaperone SDHAF4, thereby suspending complex II assembly and promoting eNOS-derived nitric oxide (NO) production. The resulting NO acts in a paracrine manner on HSCs to induce S-nitrosylation of ATG7 at cysteine 184, which in turn constraining autophagic flux and preventing HSC transdifferentiation. Our study reveals a fasting-responsive hepatocyte-stellate cell circuit that protects against liver fibrosis, highlighting the eNOS/NO/ATG7 S-nitrosylation axis as a tractable therapeutic target.

Indexed as

alternate day fastingATG7 S‐nitrosylationautophagyendothelial nitric oxide synthaseliver fibrosismitochondrial Complex II

Identifiers

PMID42801580
PMCPMC13616305

What OpenQuestion holds

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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.