ArticleNature metabolism2024
Ketogenic diet reshapes cancer metabolism through lysine β-hydroxybutyrylation.
Article in Nature metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed.
- Nuclear OXCT1 attenuates histone β-hydroxybutyrylation-mediated MHC-I transcription.Nature chemical biology · 2026Article
- Construction and validation of a β-hydroxybutyrylation-related molecular model for predicting prognosis of papillary thyroid carcinoma.Translational cancer research · 2026Article
- Ketogenic Diet as an Adjuvant in Epithelial Cancers: Mechanisms, Model Systems, and Translational Opportunities.Cancers · 2026Review
- Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.Signal transduction and targeted therapy · 2026Review
- XunZi, an AI biologist, reveals disease-modifying targets.Nature biomedical engineering · 2026Article
- Metabolic adaptations of the tumor macroenvironment and their role in cancer progression and survivorship.Genes & development · 2026Review
- RagC senses β-hydroxybutyrate abundancy to suppress mTORC1.Protein & cell · 2026Article
- Article
- Novel protein acylations in Alzheimer's disease: Molecular, mechanisms, biological significance, and diagnostic and therapeutic potentials.Journal of advanced research · 2026Review
- DeepKbhb: Context-Aware Prediction of Human Lysine β-Hydroxybutyrylation Sites.Journal of chemical information and modeling · 2026Article
- Multi-omics profiling of gut-serum axis dynamics in gestational sows with different reproductive performance.Microbiology spectrum · 2026Article
- Review
- Ketogenic diet exacerbates DSS-induced colitis through a β-hydroxybutyrate-Thomasclavelia spiroformis-γδ17 T cell axis in mice.Nature communications · 2026Article
- β-Hydroxybutyrate Attenuates Diabetic Kidney Disease Partially Via β-hydroxybutyrylation of Nrf2.Inflammation · 2026Article
- Chemical Proteomics Identifies Ketogenesis-Mediated Cysteine Modifications Regulating Redox Function.Angewandte Chemie (International ed. in English) · 2026Article
- Association Between Ketogenic Diet and Overactive Bladder: The Mediating Roles of Dietary Inflammatory Index and Weight-Adjusted Waist Index.Food science & nutrition · 2026Article
- TIGAR maintains intestinal epithelial regeneration by stabilizing HMGCL and promoting β-catenin β-hydroxybutyrylation in burn-induced sepsis.Cell death & disease · 2026Article
- Comprehensive Proteomics and β-Hydroxybutyrylation Profiling in Starvation-Induced Gastrocnemius Muscle Remodeling.Biology · 2026Article
- Targeting metabolic-epigenetic-immune axis in cancer: molecular mechanisms and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- ACADL and ADH1B signify ketone body metabolic reprogramming in osteoarthritic synovium: insights from bioinformatics and animal model studies.Frontiers in medicine · 2026Article
Corrections and comments
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Authors and funding
21 authors.
Funding
Abstract
Lysine β-hydroxybutyrylation (Kbhb) is a post-translational modification induced by the ketogenic diet (KD), a diet showing therapeutic effects on multiple human diseases. Little is known how cellular processes are regulated by Kbhb. Here we show that protein Kbhb is strongly affected by the KD through a multi-omics analysis of mouse livers. Using a small training dataset with known functions, we developed a bioinformatics method for the prediction of functionally important lysine modification sites (pFunK), which revealed functionally relevant Kbhb sites on various proteins, including aldolase B (ALDOB) Lys108. KD consumption or β-hydroxybutyrate supplementation in hepatocellular carcinoma cells increases ALDOB Lys108bhb and inhibits the enzymatic activity of ALDOB. A Kbhb-mimicking mutation (p.Lys108Gln) attenuates ALDOB activity and its binding to substrate fructose-1,6-bisphosphate, inhibits mammalian target of rapamycin signalling and glycolysis, and markedly suppresses cancer cell proliferation. Our study reveals a critical role of Kbhb in regulating cancer cell metabolism and provides a generally applicable algorithm for predicting functionally important lysine modification sites.
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Registered trials
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