Evidence mapPaperPMID 40973949Full record

ArticleLipids in health and disease2025

Liver fat mediates hippocampal-orbitofrontal reward circuit disruption and cognitive-emotional impairments in MASLD.

Liqiang Wu, Ruoyu Tang, Yidan Liang, Yihan Jin, Kuanghui Xu, Xiaofei Chen, Junping Shi, Jie Li

Erratum issuedAbstract read
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Article in Lipids in health and disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. 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

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2 · The registry

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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.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Liqiang Wu *School of Clinical Medicine, The Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, 310015, China.
Ruoyu Tang *School of Clinical Medicine, The Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, 310015, China.
Yidan LiangSchool of Clinical Medicine, The Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, 310015, China.
Yihan JinSchool of Clinical Medicine, The Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, 310015, China.
Kuanghui XuDepartment of Radiology, Zhejiang Hospital, Hangzhou, 310015, China.
Xiaofei ChenSchool of Clinical Medicine, The Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, 310015, China.
Junping ShiSchool of Clinical Medicine, The Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, 310015, China.
Jie LiSchool of Clinical Medicine, The Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, 310015, China. jie_sweethz@163.com.

Funding

Graduate Scientific Research Innovation Promotion Project of Hangzhou Normal University 2025HSDYJSKY051National Natural Science Foundation of China 82402216Project of Hangzhou Health, Science and Technology Plan A20230654Project of Zhejiang Medical and Health Science and Technology 2024KY198Zhejiang Provincial Natural Science Foundation of China LTGY24H180038
6 · The paper itself

Abstract

backgroundAs a major chronic liver condition, metabolic dysfunction-associated steatotic liver disease (MASLD) is linked to numerous extrahepatic manifestations, including cognitive and emotional dysfunction. However, its neuroanatomical and functional brain correlates remain unclear. This study investigates cerebral alterations in MASLD by examining structural differences via voxel-based morphometry (VBM), along with functional features using resting-state functional connectivity (FC). METHODS AND PATIENTS: Seventy-four MASLD patients and sixty-two demographically matched healthy controls (HC) underwent structural MRI and resting-state fMRI. Group differences in gray matter volume (GMV) and FC were analyzed using VBM and seed-based FC methods. Correlations and mediation analyses were further used to assess the relationships among abnormal GMV, altered resting-state FC and clinical indicators in MASLD individuals.

resultsPatients with MASLD exhibited reduced GMV in the bilateral hippocampus, left parahippocampal gyrus, left middle temporal gyrus, right fusiform gyrus, right supplementary motor area (SMA), and right cerebellum. Importantly, liver fat content fully mediated the effects of hippocampal atrophy on cognitive-emotional symptoms. Seed-based FC analysis further revealed decreased connectivity between the right hippocampus and the right orbitofrontal cortex. This reduction in connectivity was also associated with worse cognitive function and a higher waist-to-hip ratio.

conclusionMASLD-related brain atrophy and functional disruption are linked to visceral adiposity and neuropsychiatric deficits. The mediating role of liver fat highlights the importance of dual-pathway interventions that target both metabolic health and neural protection, potentially reducing long-term neurocognitive disability burdens and enabling accessible risk stratification in practice.

Indexed as

Cognitive DysfunctionFatty LiverHippocampusLiverPrefrontal CortexAdultCase-Control StudiesFemaleGray MatterHumansMagnetic Resonance ImagingMaleMiddle AgedRewardBrain structureCognitive functionFunctional connectivityLiver fat contentMetabolic dysfunction-associated steatotic liver diseaseVoxel-based morphometry

Identifiers

PMID40973949
PMCPMC12447603

What Socratic holds

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LicenceCC BY-NC-ND
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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 Socratic graph.