Evidence mapPaperPMID 40776473Full record

ArticleClinical and molecular hepatology2025

Hepatocytic ankyrin repeat and SOCS box protein 3 deficiency alleviates metabolic dysfunction-associated steatotic liver disease by decreasing ubiquitin-mediated carnitine palmitoyl transferase 1A.

Yuli Lin, Wulei Hou, Mengxiao Ge, Zhihao Wu, Linlin Huang, Haoye Liu, Wenli Zhang, Xiyu Deng, Lanxin Wang, Ming Guan and 3 more

Abstract read
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Article in Clinical and molecular hepatology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

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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

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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

4 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Yuli LinDepartment of Laboratory Medicine and Central Laboratory of Huashan Hospital, Fudan University, Shanghai, China.
Wulei HouDepartment of Anatomy, Histoembryology, School of Basic Medical Sciences, Fudan University, Shanghai Medical College, Shanghai, China.
Mengxiao GeDepartment of Laboratory Medicine and Central Laboratory of Huashan Hospital, Fudan University, Shanghai, China.
Zhihao WuDepartment of Immunology and Department of Anatomy, Histoembryology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Linlin HuangDepartment of Laboratory Medicine and Central Laboratory of Huashan Hospital, Fudan University, Shanghai, China.
Haoye LiuDepartment of Immunology and Department of Anatomy, Histoembryology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Wenli ZhangDepartment of Laboratory Medicine and Central Laboratory of Huashan Hospital, Fudan University, Shanghai, China.
Xiyu DengDepartment of Laboratory Medicine and Central Laboratory of Huashan Hospital, Fudan University, Shanghai, China.
Lanxin WangDepartment of Laboratory Medicine and Central Laboratory of Huashan Hospital, Fudan University, Shanghai, China.
Ming GuanDepartment of Laboratory Medicine and Central Laboratory of Huashan Hospital, Fudan University, Shanghai, China.
Chunhua SongDivision of Hematology, The Ohio State University Wexner Medical Center, the James Cancer Hospital, Columbus, OH, USA.
Zuoyun WangDepartment of Immunology and Department of Anatomy, Histoembryology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Dongqin YangDepartment of Laboratory Medicine and Central Laboratory of Huashan Hospital, Fudan University, Shanghai, China.

Funding

National Key R&D Program of China 2020YFA0803201National Key R&D Program of China 2022YFA1106400National Natural Science Foundation of China 32270886National Natural Science Foundation of China 81770579National Natural Science Foundation of China 81970506National Natural Science Foundation of China 82271800National Natural Science Foundation of China 82471775Natural Science Foundation of Shanghai 23QA1401600Natural Science Foundation of Shanghai 23ZR1413000
6 · The paper itself

Abstract

BACKGROUND/

aimsExcessive lipid accumulation in hepatocytes is a critical cause of metabolic dysfunction-associated steatotic liver disease (MASLD) progression. Ankyrin repeat and SOCS box protein 3 (ASB3) is an E3 ubiquitin ligase that mediates diverse disease processes; however, the direct substrates of ASB3 in lipid metabolism and its role in MASLD remain unexplored.

methodsWe generated ASB3 knockout mice fed a high-fat diet to induce MASLD. Oxygen consumption and fatty acid oxidation (FAO) were used to assess lipid metabolism. LC-MS/MS and IP were used to verify the ASB3 target protein. Correlation analysis was conducted on the cohort of MASLD patients vs. the control group.

resultsLoss of the ASB3 E3 ubiquitin ligase in hepatocytes strengthens mitochondrial FAO, thereby influencing energy consumption to decrease triglyceride storage and lipid accumulation. Quantitative lysine ubiquitination proteomics revealed that ASB3 directly mediated the ubiquitin levels at two sites (K180 and K639) in carnitine palmitoyl transferase 1A (CPT1A), a rate-limiting enzyme of FAO, to induce CPT1A degradation. Moreover, both constitutive and hepatocyte-specific ASB3 knockout enhance FAO and delay lipid accumulation, liver steatosis, and MASLD progression in a CPT1A-dependent manner. Hepatic ASB3 deficiency also delays fibrosis in MASLD. Analysis of public databases and liver tissue samples from MASLD patients revealed that ASB3 was highly expressed in MASLD patients and was negatively correlated with CPT1A.

conclusionOur study reveals the key roles of ASB3 in the development of MASLD and suggests a novel therapeutic potential for MASLD.

Indexed as

Carnitine O-PalmitoyltransferaseFatty LiverSuppressor of Cytokine Signaling 3 ProteinUbiquitinAnimalsDiet, High-FatDisease Models, AnimalHepatocytesHumansLipid MetabolismMaleMiceMice, Inbred C57BLMice, KnockoutUbiquitinationCarnitine O-PalmitoyltransferaseSuppressor of Cytokine Signaling 3 ProteinUbiquitinAnkyrin repeat and SOCS box protein 3Carnitine palmitoyl transferase 1AFatty acid oxidationMetabolic dysfunction-associated steatotic liver diseaseUbiquitin-proteasome system

Identifiers

PMID40776473
PMCPMC12538142

What Socratic 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 Socratic graph.