{"doi":"10.1101/2024.12.18.628574","title":"Ketone body mediated histone β-hydroxybutyrylation is reno-protective","abstract":"Abstract Starvation, intermittent fasting and exercise, all of which are recommended lifestyle modifiers share a common metabolic signature, ketogenesis to generate the ketone bodies, predominantly β-hydroxybutyrate. β-hydroxybutyrate exerts beneficial effects across various contexts, preventing or mitigating disease. We hypothesized that these dynamic health benefits of β-hydroxybutyrate might stem from its ability to regulate genome architecture through chromatin remodeling via histone β-hydroxybutyrylation, thereby influencing the transcriptome. Focusing on the kidney, which is an end organ protected by β-hydroxybutyrate, we examined histone β-hydroxybutyrylation-mediated chromatin remodeling. Notably, regions of the genome associated with lipid catabolism were predominantly in an open chromatin configuration, leading to active transcription and translation. Significant β-hydroxybutyrylation was observed in the kidneys and the most highly upregulated gene actively transcribed and translated was 3-hydroxy-3-methyglutaryl CoA Synthase 2 ( Hmgcs2 ), a gene responsible for the biosynthesis of β-hydroxybutyrate in mitochondria. In contrast, regions with more compact chromatin structures were enriched with genes related to immune function such as protein tyrosine phosphatase receptor type C ( Ptprc ) and lymphocyte cytosolic protein 1 ( Lcp1 ), which exhibited reduced transcription and translation. These results reveal that renal epigenetic histone β-hydroxybutyrylation is a novel mechanism by which transcriptional regulation of both energy metabolism and immune function occur concomitantly to protect kidneys and lower hypertension. Abstract Figure Graphical Abstract","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":492707,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9569,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":798415,"name":"Sachin Aryal","orcid":"0000-0002-1939-6338","position":1,"is_corresponding":false},{"id":798413,"name":"Ishan Manandhar","orcid":"0000-0001-6772-2540","position":2,"is_corresponding":false},{"id":298822,"name":"Saroj Chakraborty","orcid":"0000-0002-8728-8187","position":3,"is_corresponding":false},{"id":298825,"name":"Xue Mei","orcid":"0000-0001-7547-5746","position":4,"is_corresponding":false},{"id":278270,"name":"Beng San Yeoh","orcid":"0000-0002-7723-8733","position":5,"is_corresponding":false},{"id":298823,"name":"Blair Mell","orcid":"0000-0002-1224-4948","position":6,"is_corresponding":false},{"id":444131,"name":"Andrew L. Kleinhenz","orcid":"0000-0002-7088-0088","position":7,"is_corresponding":false},{"id":914233,"name":"Ramakumar Tummala","orcid":"0000-0002-3887-3566","position":8,"is_corresponding":false},{"id":298821,"name":"Tao Yang","orcid":"0000-0002-4182-9793","position":9,"is_corresponding":false},{"id":278269,"name":"Piu Saha","orcid":"0000-0003-0626-398X","position":10,"is_corresponding":false},{"id":850964,"name":"William T. Gunning","orcid":"0000-0002-4190-2479","position":11,"is_corresponding":false},{"id":278273,"name":"Matam Vijay–Kumar","orcid":"0000-0002-8732-0167","position":12,"is_corresponding":false},{"id":253569,"name":"Venkatesha Basrur","orcid":"0000-0002-0853-9655","position":13,"is_corresponding":false},{"id":340734,"name":"Ivana de la Serna","orcid":null,"position":14,"is_corresponding":false},{"id":278272,"name":"Bina Joe","orcid":"0000-0002-2385-7061","position":15,"is_corresponding":false},{"id":300264,"name":"Juthika Mandal","orcid":null,"position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-19T02:08:56.210382Z","pmid":"39763881","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}