Evidence map›Paper›PMID 39629559›Full record

ArticleCirculation research2025

GSK3β Deficiency Expands Obese Adipose Vasculature to Mitigate Metabolic Disorders.

Li Wang, Jiajia Li, Ping Tang, Dongliang Zhu, Lixin Tai, Yuan Wang, Tsukiko Miyata, James R Woodgett, Li-Jun Di

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In one paragraph

Article in Circulation research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Li WangDepartment of Biomedical Sciences, Faculty of Health Sciences (L.W., J.L., P.T., D.Z., L.T., Y.W., L.D.), University of Macau, China.
Jiajia LiDepartment of Biomedical Sciences, Faculty of Health Sciences (L.W., J.L., P.T., D.Z., L.T., Y.W., L.D.), University of Macau, China.
Ping TangDepartment of Biomedical Sciences, Faculty of Health Sciences (L.W., J.L., P.T., D.Z., L.T., Y.W., L.D.), University of Macau, China.
Dongliang ZhuDepartment of Biomedical Sciences, Faculty of Health Sciences (L.W., J.L., P.T., D.Z., L.T., Y.W., L.D.), University of Macau, China.ORCID 0000-0001-9612-4478
Lixin TaiDepartment of Biomedical Sciences, Faculty of Health Sciences (L.W., J.L., P.T., D.Z., L.T., Y.W., L.D.), University of Macau, China.
Yuan WangDepartment of Biomedical Sciences, Faculty of Health Sciences (L.W., J.L., P.T., D.Z., L.T., Y.W., L.D.), University of Macau, China.
Tsukiko MiyataLunenfeld-Tanenbaum Research Institute, Sinai Health and Department of Medical Biophysics, University of Toronto, Ontario, Canada (T.M., J.R.W.).ORCID 0009-0006-5256-5822
James R WoodgettLunenfeld-Tanenbaum Research Institute, Sinai Health and Department of Medical Biophysics, University of Toronto, Ontario, Canada (T.M., J.R.W.).ORCID 0000-0003-3731-5797
Li-Jun DiDepartment of Biomedical Sciences, Faculty of Health Sciences (L.W., J.L., P.T., D.Z., L.T., Y.W., L.D.), University of Macau, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMaintaining a well-developed vascular system alongside adipose tissue (AT) expansion significantly reduces the risk of metabolic complications. Although GSK3β (glycogen synthase kinase-3 beta) is known for its role in various cellular processes, its specific functions in AT and regulation of body homeostasis have not been reported.

methodsGSK3β-floxed and GSK3α-floxed mice were crossed with adiponectin-Cre mice to generate GSK3β or GSK3α adipocyte-specific knockout mice (GSK3β

resultsOur findings provide the first evidence that adipocyte-specific knockout of GSK3β expands AT vascularization and mitigates obesity-related metabolic disorders. GSK3β deficiency, but not GSK3α, in adipocytes activates AMPK (AMP-activated protein kinase), leading to increased phosphorylation and nuclear accumulation of HIF-2α, resulting in enhanced transcriptional regulation. Consequently, adipocytes increased VEGF (vascular endothelial growth factor) expression, which engages VEGFR2 on endothelial cells, promoting angiogenesis, expanding the vasculature, and improving vessel perfusion within obese AT. GSK3β deficiency promotes AT remodeling, shifting unhealthy adipocyte function toward a healthier state by increasing insulin-sensitizing hormone adiponectin and preserving healthy adipocyte function. These effects lead to reduced fibrosis, reactive oxygen species, and ER (endoplasmic reticulum) stress in obese AT and improve metabolic disorders associated with obesity.

conclusionsDeletion of GSK3β in adipocytes activates the AMPK/HIF-2α/VEGF/VEGFR2 axis, promoting vasculature expansion within obese AT. This results in a significantly improved local microenvironment, reducing inflammation and effectively ameliorating metabolic disorders associated with obesity.

Indexed as

Adipose TissueGlycogen Synthase Kinase 3 betaMice, KnockoutObesityAdipocytesAnimalsCells, CulturedDiet, High-FatEndothelial CellsMaleMetabolic DiseasesMiceMice, Inbred C57BLGlycogen Synthase Kinase 3 betaGsk3b protein, mouseglycogen synthase kinase 3 betaobesityvascular endothelial growth factor A

Identifiers

PMID39629559
PMCPMC11692787

What Socratic 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 Socratic graph.