ArticleFrontiers of medicine2023
Sodium butyrate activates HMGCS2 to promote ketone body production through SIRT5-mediated desuccinylation.
Article in Frontiers of medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- Perilipin 2 drives cisplatin-induced acute kidney injury in young but not aged kidneys.American journal of physiology. Renal physiology · 2026Article
- The Trajectory of Epigenetic Chromatin Remodeling in Cardiometabolic Disease and its Therapeutic Implications.Journal of cardiovascular translational research · 2026Review
- Single-cell and experimental analyses identify mitochondria-related genes Hmgcs2, Nudt5, and Cpt1c in painful diabetic peripheral neuropathy.Scientific reports · 2026Article
- Beyond deacetylation: crosstalk mechanisms and context-dependent regulation of sirtuin non-classical enzymatic functions in disease.Molecular medicine (Cambridge, Mass.) · 2026Review
- Succinylation modification in diabetes and diabetic complications: Mechanisms and functions (Review).Molecular medicine reports · 2026Review
- Epigenetic orchestrator and drug enhancer: dual roles of butyrate in regulating post-translational modification and optimizing therapeutic delivery.Cell communication and signaling : CCS · 2025Review
- Identification and validation of SQLE in steroid-induced osteonecrosis of the femoral head: a bioinformatics and experimental study.Journal of orthopaedic surgery and research · 2025Article
- Resveratrol Alleviated Oxidative Damage of Bovine Mammary Epithelial Cells via Activating SIRT5-IDH2 Axis.Antioxidants (Basel, Switzerland) · 2025Article
- Metabolic syndrome in colorectal cancer liver metastasis: metabolic reprogramming and microenvironment crosstalk.Frontiers in immunology · 2025Review
- Mitochondrial dysfunction as a therapeutic nexus in HFpEF: therapeutic target and pharmacological advances.Frontiers in pharmacology · 2025Review
- Multimodal diagnostic models and subtype analysis for neoadjuvant therapy in breast cancer.Frontiers in immunology · 2025Article
- Review
- Article
- Butyrate suppresses experimental necrotizing enterocolitis-induced brain injury in mice.Frontiers in pediatrics · 2023Article
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Authors and funding
14 authors at 8 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ketone bodies have beneficial metabolic activities, and the induction of plasma ketone bodies is a health promotion strategy. Dietary supplementation of sodium butyrate (SB) is an effective approach in the induction of plasma ketone bodies. However, the cellular and molecular mechanisms are unknown. In this study, SB was found to enhance the catalytic activity of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), a rate-limiting enzyme in ketogenesis, to promote ketone body production in hepatocytes. SB administrated by gavage or intraperitoneal injection significantly induced blood ß-hydroxybutyrate (BHB) in mice. BHB production was induced in the primary hepatocytes by SB. Protein succinylation was altered by SB in the liver tissues with down-regulation in 58 proteins and up-regulation in 26 proteins in the proteomics analysis. However, the alteration was mostly observed in mitochondrial proteins with 41% down- and 65% up-regulation, respectively. Succinylation status of HMGCS2 protein was altered by a reduction at two sites (K221 and K358) without a change in the protein level. The SB effect was significantly reduced by a SIRT5 inhibitor and in Sirt5-KO mice. The data suggests that SB activated HMGCS2 through SIRT5-mediated desuccinylation for ketone body production by the liver. The effect was not associated with an elevation in NAD
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