ArticleJCI insight2021
Brd4 modulates diet-induced obesity via PPARγ-dependent Gdf3 expression in adipose tissue macrophages.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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The trial behind it
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Who cites it
25 citing papers in PubMed, 30 citations in OpenAlex.
- Apabetalone Drives a Metabolic Shift Towards Ketogenesis and Reduces Liver Steatosis in Diet-Induced Obesity Mice.Biomedicines · 2026Article
- Targeting bromodomain and extraterminal proteins in cardiovascular disease: Pathological mechanisms and therapeutic applications.The Journal of international medical research · 2026Review
- FXR and BET signaling orchestrate to protect β cells.bioRxiv : the preprint server for biology · 2026Article
- BRD4 modulates antimicrobial defense via non-canonical NRF2 activation in macrophages to confer protection against sepsis.PLoS pathogens · 2026Article
- Article
- Serum GDF3 is Associated with Visceral Obesity, Insulin Resistance, and Inflammation in Non-Diabetic Adults: A Cross-Sectional Study with an Interventional Component.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Article
- GDF3 promotes adipose tissue macrophage-mediated inflammation via altered chromatin accessibility during aging.Nature aging · 2026Article
- I-BET151 modulates glucokinase gene expression and beta cell function in part through changes in FOXO1 expression.Diabetologia · 2025Article
- Dose-dependent effects of cannabidiol in drinking water on yolk fatty acid profile and hepatic expression of polyunsaturated fatty acids (PUFAs) -related genes in laying hens: insights into the cannabidiol (CBD) systemic and molecular mechanisms of action.BMC veterinary research · 2025Article
- Deletion of EP3 prostaglandin receptor in murine macrophages aggravates diet-induced obesity by suppressing SPARC.The EMBO journal · 2025Article
- Type 2 diabetes mellitus - conventional therapies and future perspectives in innovative treatment.Biochemistry and biophysics reports · 2025Review
- Acute regulation of murine adipose tissue lipolysis and insulin resistance by the TGFβ superfamily protein GDF3.Nature communications · 2025Article
- Brd4 modulates metabolic endotoxemia-induced inflammation by regulating colonic macrophage infiltration in high-fat diet-fed mice.Communications biology · 2024Article
- Targeting BRD4 mitigates hepatocellular lipotoxicity by suppressing the NLRP3 inflammasome activation and GSDMD-mediated hepatocyte pyroptosis.Cellular and molecular life sciences : CMLS · 2024Article
- Novel BRD4-p53 Inhibitor SDU-071 Suppresses Proliferation and Migration of MDA-MB-231 Triple-Negative Breast Cancer Cells.ACS pharmacology & translational science · 2024Article
- GDF3 Protects Mice against Sepsis-Induced Acute Lung Injury by Suppression of Macrophage Pyroptosis.Pharmaceuticals (Basel, Switzerland) · 2024Article
- BRD4 Regulates Glycolysis-Dependent Nos2 Expression in Macrophages Upon H pylori Infection.Cellular and molecular gastroenterology and hepatology · 2024Article
- Transcriptional co-activators: emerging roles in signaling pathways and potential therapeutic targets for diseases.Signal transduction and targeted therapy · 2023Review
- A novel multifunctional radioprotective strategy using P7C3 as a countermeasure against ionizing radiation-induced bone loss.Bone research · 2023Article
- Obesity-Linked PPARγ Ser273 Phosphorylation Promotes Beneficial Effects on the Liver, despite Reduced Insulin Sensitivity in Mice.Biomolecules · 2023Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
Macrophage-mediated inflammatory response has been implicated in the pathogenesis of obesity and insulin resistance. Brd4 has emerged as a key regulator in the innate immune response. However, the role of Brd4 in obesity-associated inflammation and insulin resistance remains uncharacterized. Here, we demonstrated that myeloid lineage-specific Brd4 knockout (Brd4-CKO) mice were protected from high-fat diet-induced (HFD-induced) obesity with less fat accumulation, higher energy expenditure, and increased lipolysis in adipose tissue. Brd4-CKO mice fed a HFD also displayed reduced local and systemic inflammation with improved insulin sensitivity. RNA-Seq of adipose tissue macrophages (ATMs) from HFD-fed WT and Brd4-CKO mice revealed that expression of antilipolytic factor Gdf3 was significantly decreased in ATMs of Brd4-CKO mice. We also found that Brd4 bound to the promoter and enhancers of Gdf3 to facilitate PPARγ-dependent Gdf3 expression in macrophages. Furthermore, Brd4-mediated expression of Gdf3 acted as a paracrine signal targeting adipocytes to suppress the expression of lipases and the associated lipolysis in cultured cells and mice. Controlling the expression of Gdf3 in ATMs could be one of the mechanisms by which Brd4 modulates lipid metabolism and diet-induced obesity. This study suggests that Brd4 could be a potential therapeutic target for obesity and insulin resistance.
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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.