ArticleCell death & disease2024
β-Hydroxybutyrate suppresses M1 macrophage polarization through β-hydroxybutyrylation of the STAT1 protein.
Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Ketogenesis as a Metabolic Checkpoint in MASLD: Implications for Disease Progression and Therapy.Metabolites · 2026Review
- β-hydroxybutyrate as an early predictive biomarker of diabetes remission following intensive dietary intervention.Endocrine · 2026Article
- Effects of β‑hydroxybutyrate on restoring autophagic flux and mitochondrial function in macrophages exposed to oxidized low‑density lipoprotein.Molecular medicine reports · 2026Article
- Myeloid PKM2 deficiency alleviates allergic airway inflammation and promotes macrophage efferocytosis via SLC13A3.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Association Between Endogenous Ketosis and Risk of Atrial Fibrillation in Intensive Care Versus General Ward Patients: A Retrospective Cohort Study.Journal of clinical medicine · 2026Article
- Metabolic Perspective on Atherosclerosis: Macrophage Reprogramming and Novel Therapeutic Targets.Journal of the American Heart Association · 2026Review
- TRIM26 deficiency promotes liver fibrosis progression by mediating macrophage polarization via the EZH2-STAT1 axis.Hepatology international · 2026Article
- β-Hydroxybutyrate Attenuates Diabetic Kidney Disease Partially Via β-hydroxybutyrylation of Nrf2.Inflammation · 2026Article
- More than Glucose Elimination: Additional Benefits of SGLT2 Inhibitors in Glomerular Diseases.Drugs · 2026Review
- Liver-specific delivery of MDM2 antisense oligonucleotides counteracts diet-induced metabolic-dysfunction-associated steatotic liver diseases.Molecular therapy. Nucleic acids · 2026Article
- Ketogenic diet sex-dependent effects on rat bone marrow cells during development and β-HB protection in hypoglycemia.Scientific reports · 2026Article
- Review
- Hepatic HMGCS2-derived β-hydroxybutyrate attenuates hippocampal insulin resistance and neuroinflammation to promote MASLD-induced cognitive function.Communications biology · 2026Article
- Advances in traditional Chinese medicine for modulating macrophage polarization in the treatment of rheumatoid arthritis.Frontiers in pharmacology · 2026Review
- CAF-derived BHB modulates FXR1-Kbhb and NK-cell lipid metabolism in osteosarcoma.International journal of biological sciences · 2026Article
- Regulatory Landscapes of Protein Acylations in Neuroinflammation: From Molecular Mechanisms to Therapeutic Targets.Neurochemical research · 2025Review
- β-Hydroxybutyrate ameliorates lipopolysaccharide-induced liver injury through β-hydroxybutyrylation of the SOD2 protein in mice.Redox biology · 2025Article
- Metabolic reprogramming of immune cells in the battle against intracellular bacterial chronic infections: novel mechanisms and breakthroughs.Molecular biology reports · 2025Review
- Engineering macrophages for targeted immunotherapy and drug delivery in melanoma.Journal of translational medicine · 2025Review
- Transient Dietary Intervention Induces Healthy Adipose Tissue Expansion and Metabolically Healthy Obesity in Mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
Corrections and comments
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Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
β-Hydroxybutyrate (β-OHB), the primary ketone body, is a bioactive metabolite that acts as both an energy substrate and a signaling molecule. Recent studies found that β-OHB inhibits the production of pro-inflammatory cytokines in macrophages, but its underlying molecular mechanisms have not yet been fully elucidated. Lysine β-hydroxybutyrylation (Kbhb), a post-translational modification mediated by β-OHB, plays a key role in regulating the expression and activity of modified proteins. However, whether macrophages undergo protein Kbhb and whether Kbhb modification regulates macrophage polarization remains largely unknown. In this study, treatment with β-OHB and ketone ester significantly decreased the lipopolysaccharide (LPS)-induced enhancement of the M1 phenotype of mouse bone marrow-derived macrophages (BMDMs), RAW264.7 cells, and peritoneal macrophages (PMs) in vitro and in vivo. Moreover, β-OHB treatment induced global protein Kbhb, which is associated with the regulation of macrophage M1 polarization. Proteome-wide Kbhb analysis in β-OHB-treated BMDMs revealed 3469 Kbhb modification sites within 1549 proteins, among which interleukin-12-responding proteins were significantly upregulated. Our results indicated that β-OHB regulated M1 macrophage polarization by inducing Kbhb modification of the signal transducer and activator of transcription 1 (STAT1) K679 site, which inhibited its LPS-induced phosphorylation and transcription. Altogether, our study demonstrated the presence of a widespread Kbhb landscape in the β-OHB-treated macrophages and provided novel insights into the anti-inflammatory effects of β-OHB.
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