Evidence map›Paper›PMID 40983918›Full record

ArticleBMC medicine2025

Inhibition of GCKIII kinases STK25 and MST3 mitigates organ lipotoxicity and enhances metabolic resilience under nutritional stress.

Emma Andersson, Xiangdong Gongye, Emmelie Cansby, Jingjing Zhang, Mara Caputo, Bernice Asiedu, Viktor Garellick, Sheri Booten, Sue Murray, Ferran Font-Gironès and 6 more

Abstract read
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In one paragraph

Article in BMC medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. 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

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

2 citing papers in PubMed.

  1. Article
  2. Article
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

16 authors.

Emma AnderssonDepartment of Chemistry and Molecular Biology, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.
Xiangdong GongyeDepartment of Chemistry and Molecular Biology, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.
Emmelie CansbyDepartment of Chemistry and Molecular Biology, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.
Jingjing ZhangDepartment of Chemistry and Molecular Biology, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.
Mara CaputoDepartment of Chemistry and Molecular Biology, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.
Bernice AsieduDepartment of Chemistry and Molecular Biology, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.
Viktor GarellickDepartment of Chemistry and Molecular Biology, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.
Sheri BootenIonis Pharmaceuticals, Carlsbad, CA, USA.
Sue MurrayIonis Pharmaceuticals, Carlsbad, CA, USA.
Ferran Font-GironèsDepartment of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Johan RuudDepartment of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Dan Emil LindDepartment of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburgand, Sahlgrenska University Hospital , Gothenburg, Sweden.
Manoj AmrutkarDepartment of Pathology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
Brian W HowellDepartment of Neuroscience and Physiology, State University of New York Upstate Medical University, Syracuse, NY, USA.
Ingrid Wernstedt AsterholmDepartment of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Margit MahlapuuDepartment of Chemistry and Molecular Biology, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden. margit.mahlapuu@gu.se.

Funding

Swedish state under the agreement between the Swedish Government and the county councils, the ALF-agreement ALFGBG-1005122
6 · The paper itself

Abstract

backgroundObesity has reached pandemic proportions, highlighting the urgent need for continued research to uncover the molecular mechanisms governing lipid homeostasis and ectopic fat deposition in overnutrition. Our recent translational studies demonstrated that STE20-type kinases STK25 and MST3 associate with intracellular lipid droplets and play a pivotal role in regulating the dynamic balance between fat storage and utilization. This study aimed to assess the in vivo effects of the combined inhibition of STK25 and MST3 in obese mice.

methodsWe performed phenotypic characterization in three cohorts of mice fed a high-fat diet: (1) mice with genetic ablation of Stk25, (2) mice treated with Mst3-targeting antisense oligonucleotide (ASO), and (3) mice depleted of both STK25 and MST3 by injecting Stk25

resultsWe found that the inactivation of STK25 and MST3, either individually or in combination, provided equal protection against ectopic fat accumulation and associated lipotoxic damage in the liver, kidney, and skeletal muscle of obese mice. Strikingly, high-fat diet-fed STK25/MST3-deficient mice, but not mice lacking only one kinase, displayed reduced body and fat mass gain, which was accompanied by markedly increased abundance of thermogenesis markers in the brown adipose tissue (BAT).

conclusionsDual inhibition of STK25 and MST3 in mice mitigates obesity-triggered lipotoxic injury to metabolic tissues and elevates indicators of BAT thermogenic capacity.

Indexed as

Intracellular Signaling Peptides and ProteinsObesityProtein Serine-Threonine KinasesSerine-Threonine Kinase 3AnimalsDiet, High-FatHippo KinasesLipid MetabolismLiverMaleMiceMice, Inbred C57BLMice, KnockoutOligonucleotides, AntisenseHippo KinasesIntracellular Signaling Peptides and ProteinsOligonucleotides, AntisenseProtein Serine-Threonine KinasesSerine-Threonine Kinase 3Stk25 protein, mouseLipotoxicityObesityOxidative phosphorylationThermogenic capacity

Identifiers

PMID40983918
PMCPMC12455811

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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.