Evidence map›Paper›PMID 40341440›Full record

ArticleNature communications2025

Hepatic AKAP1 deficiency exacerbates diet-induced MASLD by enhancing GPAT1-mediated lysophosphatidic acid synthesis.

Linjie He, Xiaojuan She, Lifei Guo, Mingshu Gao, Shuangbin Wang, Zhenxing Lu, Haitao Guo, Renlong Li, Yongzhan Nie, Jinliang Xing and 1 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

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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

11 authors.

Linjie He *State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and Department of Physiology and Pathophysiology, Fourth Military Medical University, Xi'an, Shaanxi, China.
Xiaojuan She *State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and Department of Physiology and Pathophysiology, Fourth Military Medical University, Xi'an, Shaanxi, China.
Lifei GuoState Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and Department of Physiology and Pathophysiology, Fourth Military Medical University, Xi'an, Shaanxi, China.
Mingshu GaoCollege of Life Sciences, Northwest University, Xi'an, Shaanxi, China.
Shuangbin WangNational Demonstration Center for Experimental Basic Medical Science Education, Fourth Military Medical University, Xi'an, Shaanxi, China.
Zhenxing LuState Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and Department of Physiology and Pathophysiology, Fourth Military Medical University, Xi'an, Shaanxi, China.
Haitao GuoState Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and Department of Physiology and Pathophysiology, Fourth Military Medical University, Xi'an, Shaanxi, China.
Renlong LiState Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi, China.
Yongzhan NieState Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi, China.ORCID http://orcid.org/0000-0003-1124-4548
Jinliang XingState Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and Department of Physiology and Pathophysiology, Fourth Military Medical University, Xi'an, Shaanxi, China. xingjl@fmmu.edu.cn.ORCID http://orcid.org/0000-0001-8979-2056
Lele JiNational Demonstration Center for Experimental Basic Medical Science Education, Fourth Military Medical University, Xi'an, Shaanxi, China. jilele@fmmu.edu.cn.ORCID http://orcid.org/0000-0003-4200-7780

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD), closely associated with obesity, can progress to metabolic dysfunction-associated steatohepatitis when the liver undergoes overt inflammatory damage. A-kinase anchoring protein 1 (AKAP1) has been shown to control lipid accumulation in brown adipocytes. However, the role of AKAP1 signaling in hepatic lipid metabolism and MASLD remains poorly understood. Here, we showed that hepatocyte-specific AKAP1 deficiency exacerbated hepatic steatosis and steatohepatitis in male mice subjected to a high-fat diet and fast-food diet, respectively. Mechanistically, AKAP1 directly phosphorylated and inactivated glycerol-3-phosphate acyltransferase 1 (GPAT1) in a PKA-dependent manner, thus suppressing lysophosphatidic acid (LPA) production. Increased endogenous LPA in hepatocytes promoted hepatocellular triglyceride (TG) synthesis and initiated pronounced inflammatory response in Kupffer cells. Restoring hepatic AKAP1 or repressing LPA levels via GPAT1 knockdown alleviated MASLD exacerbation. Overall, AKAP1 plays a protective role against MASLD by inhibiting GPAT1 activity, highlighting the potential of targeting AKAP1/PKA/GPAT1 signalosome for MASLD therapy.

Indexed as

A Kinase Anchor ProteinsFatty LiverGlycerol-3-Phosphate O-AcyltransferaseLiverLysophospholipidsAnimalsCyclic AMP-Dependent Protein KinasesDiet, High-FatHepatocytesHumansKupffer CellsMaleMiceMice, Inbred C57BLMice, KnockoutSignal TransductionA Kinase Anchor ProteinsCyclic AMP-Dependent Protein KinasesGlycerol-3-Phosphate O-Acyltransferaselysophosphatidic acidLysophospholipidsTriglycerides

Identifiers

PMID40341440
PMCPMC12062205

What OpenQuestion holds

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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 OpenQuestion graph.