Evidence mapPaperPMID 40760121Full record

ArticleThe EMBO journal2025

Hepatic ASPG-mediated lysophosphatidylinositol catabolism impairs insulin signal transduction.

Feiyan Li, Hua-Sheng Huang, Qingwen Zhao, Wei Zhang, Ting Shi, Wenjing Lv, Qi Zhu, Haojie Liu, Yingjiang Xu, Haiyan Huang and 4 more

Abstract read
In one paragraph

Article in The EMBO journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Review
  2. Article
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  5. Review
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.

Feiyan LiKey Laboratory of Metabolism and Molecular Medicine of the Ministry of Education; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences; Fudan University, 200032, Shanghai, China.ORCID http://orcid.org/0009-0005-9801-4172
Hua-Sheng HuangDepartment of Hepatobiliary Surgery, the First Affiliated Hospital of Guangxi Medical University, 530021, Nanning, China.
Qingwen ZhaoZhejiang Key Laboratory of Traditional Chinese Medicine for the Prevention and Treatment of Senile Chronic Diseases, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, 310006, Hangzhou, China.ORCID http://orcid.org/0000-0003-3318-6545
Wei ZhangKey Laboratory of Metabolism and Molecular Medicine of the Ministry of Education; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences; Fudan University, 200032, Shanghai, China.
Ting ShiKey Laboratory of Metabolism and Molecular Medicine of the Ministry of Education; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences; Fudan University, 200032, Shanghai, China.ORCID http://orcid.org/0009-0004-3152-2124
Wenjing LvKey Laboratory of Metabolism and Molecular Medicine of the Ministry of Education; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences; Fudan University, 200032, Shanghai, China.
Qi ZhuKey Laboratory of Metabolism and Molecular Medicine of the Ministry of Education; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences; Fudan University, 200032, Shanghai, China.
Haojie LiuKey Laboratory of Metabolism and Molecular Medicine of the Ministry of Education; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences; Fudan University, 200032, Shanghai, China.ORCID http://orcid.org/0000-0002-9289-3322
Yingjiang XuDepartment of Interventional Vascular Surgery, Binzhou Medical University Hospital, Binzhou, Shandong, China.
Haiyan HuangKey Laboratory of Metabolism and Molecular Medicine of the Ministry of Education; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences; Fudan University, 200032, Shanghai, China.
Qi-Qun TangKey Laboratory of Metabolism and Molecular Medicine of the Ministry of Education; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences; Fudan University, 200032, Shanghai, China.ORCID http://orcid.org/0000-0002-0285-7425
Yue GaoZhejiang Key Laboratory of Traditional Chinese Medicine for the Prevention and Treatment of Senile Chronic Diseases, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, 310006, Hangzhou, China.
Tao PengDepartment of Hepatobiliary Surgery, the First Affiliated Hospital of Guangxi Medical University, 530021, Nanning, China.
Dongning PanKey Laboratory of Metabolism and Molecular Medicine of the Ministry of Education; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences; Fudan University, 200032, Shanghai, China. dongning.pan@fudan.edu.cn.ORCID http://orcid.org/0000-0001-5463-8155

Funding

MOST | National Natural Science Foundation of China (NSFC) 32471356,32171140MOST | National Natural Science Foundation of China (NSFC) 82200981MOST | National Natural Science Foundation of China (NSFC) 82400940Special Funds of Taishan Scholars Project of Shandong Province TSQN202312384STCSM | Program of Shanghai Academic Research Leader (Shanghai Academic Research Leader) 22XD1400500
6 · The paper itself

Abstract

Bioactive glycerolysophospholipids (GLPs) are implicated in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) and obesity; however, the mechanisms underlying glycerolysophospholipid-mediated changes in insulin signaling remain poorly understood. Here, we identify the amino acid-metabolism enzyme asparaginase (ASPG) as a critical regulator of systemic fatty acid handling and insulin signal transduction. Hepatic ASPG expression levels negatively correlate with insulin sensitivity in humans. Loss of Aspg in MASLD mice modifies the liver hepatokine secretome, enhancing systemic insulin sensitivity. Notably, ASPG bears lysophospholipase activity towards the bioactive lipid lysophosphatidylinositol (LPI) in vitro and in vivo. Mechanistically, Aspg deficiency results in accumulation of intracellular LPIs and consequently in suppression of tyrosine phosphatase PTP1B activity. This in turn decreases FOXO1-dependent expression of the hepatokine Sepp1, leading to reduced SEPP1 secretion and extrahepatic insulin-sensitization. In summary, this study uncovers a novel biological mechanism whereby ASPG-controlled bioactive lipid levels modulate insulin resistance and insulin secretion, suggesting complementary therapeutic strategies for the improvement of systemic glucose homeostasis.

Indexed as

InsulinLiverLysophospholipidsSignal TransductionAnimalsFatty LiverForkhead Box Protein O1HumansInsulin ResistanceMaleMiceMice, Inbred C57BLMice, KnockoutProtein Tyrosine Phosphatase, Non-Receptor Type 1Forkhead Box Protein O1InsulinlysophosphatidylinositolLysophospholipidsProtein Tyrosine Phosphatase, Non-Receptor Type 1Ptpn1 protein, mouseASPGInsulin SignalingLysophosphatidylinositolLysophospholipasePTP1B

Identifiers

PMID40760121
PMCPMC12436650

What Socratic holds

Textmetadata
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 Socratic graph.