ArticleNature medicine2016
Loss of the co-repressor GPS2 sensitizes macrophage activation upon metabolic stress induced by obesity and type 2 diabetes.
Article in Nature medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.
- Histone and Histone Acetylation-Related Alterations of Gene Expression in Uninvolved Psoriatic Skin and Their Effects on Cell Proliferation, Differentiation, and Immune Responses.International journal of molecular sciences · 2023Pooled it
- GPS2 regulates embryonic angiogenesis by enhancing endothelial cell survival through stabilizing HOIP.Cell death and differentiation · 2026Article
- ALKBH5 facilitates Srgn stability via m6A demethylation to disrupt blood-testis barrier integrity in the high-fat diet mice.Cellular and molecular life sciences : CMLS · 2026Article
- Sex-specific KDM6A-HNF4A-CREBH network controls lipoprotein cholesterol metabolism and atherosclerosis via epigenetic reprograming of hepatocytes.Nature communications · 2026Article
- Tissue-resident macrophage survival depends on mitochondrial function regulated by SerpinB2 in chronic inflammation.Nature communications · 2026Article
- Nuclear receptor coregulator interactions: beyond the switch.Genes & development · 2026Review
- SMRT anchors the HDAC3 corepressor complex to chromatin to regulate inflammatory and metabolic pathways in macrophages.Nucleic acids research · 2025Article
- Nonproteolytic ubiquitination regulates chromatin occupancy by the NCoR/SMRT/HDAC3 corepressor complex in MCF-7 breast cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- GPS2 promotes erythroid differentiation in K562 erythroleukemia cells primarily via NCOR1.International journal of hematology · 2024Article
- GPS2 ameliorates cigarette smoking-induced pulmonary vascular remodeling by modulating the ras-Raf-ERK axis.Respiratory research · 2024Article
- The histone methyltransferase ASH1L protects against bone loss by inhibiting osteoclastogenesis.Cell death and differentiation · 2024Article
- LncRNA LINK-A Remodels Tissue Inflammatory Microenvironments to Promote Obesity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- FXR Friend-ChIPs in the Enterohepatic System.Seminars in liver disease · 2023Review
- Insights into the Role of Plasmatic and Exosomal microRNAs in Oxidative Stress-Related Metabolic Diseases.Antioxidants (Basel, Switzerland) · 2023Review
- Macrophage function in adipose tissue homeostasis and metabolic inflammation.Nature immunology · 2023Review
- Antagonistic action of GPS2 and KDM1A at enhancers governs alternative macrophage activation by interleukin 4.Nucleic acids research · 2023Article
- The PI3K/Akt Pathway in Meta-Inflammation.International journal of molecular sciences · 2022Review
- Protein palmitoylation-mediated palmitic acid sensing causes blood-testis barrier damage via inducing ER stress.Redox biology · 2022Article
- Helminth infection modulates number and function of adipose tissue Tregs in high fat diet-induced obesity.PLoS neglected tropical diseases · 2022Article
- The Role of T Cells in Obesity-Associated Inflammation and Metabolic Disease.Immune network · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Humans with obesity differ in their susceptibility to developing insulin resistance and type 2 diabetes (T2D). This variation may relate to the extent of adipose tissue (AT) inflammation that develops as their obesity progresses. The state of macrophage activation has a central role in determining the degree of AT inflammation and thus its dysfunction, and these states are driven by epigenomic alterations linked to gene expression. The underlying mechanisms that regulate these alterations, however, are poorly defined. Here we demonstrate that a co-repressor complex containing G protein pathway suppressor 2 (GPS2) crucially controls the macrophage epigenome during activation by metabolic stress. The study of AT from humans with and without obesity revealed correlations between reduced GPS2 expression in macrophages, elevated systemic and AT inflammation, and diabetic status. The causality of this relationship was confirmed by using macrophage-specific Gps2-knockout (KO) mice, in which inappropriate co-repressor complex function caused enhancer activation, pro-inflammatory gene expression and hypersensitivity toward metabolic-stress signals. By contrast, transplantation of GPS2-overexpressing bone marrow into two mouse models of obesity (ob/ob and diet-induced obesity) reduced inflammation and improved insulin sensitivity. Thus, our data reveal a potentially reversible disease mechanism that links co-repressor-dependent epigenomic alterations in macrophages to AT inflammation and the development of T2D.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.