β-羟基丁酸：远不止是一种代谢产物。
β-hydroxybutyrate: much more than a metabolite.
作者信息
Newman John C, Verdin Eric
机构信息
Division of Geriatrics, University of California San Francisco, San Francisco, CA, USA; Gladstone Institutes, University of California San Francisco, 1650 Owens St., San Francisco, CA 94158, USA.
Gladstone Institutes, University of California San Francisco, 1650 Owens St., San Francisco, CA 94158, USA.
出版信息
Diabetes Res Clin Pract. 2014 Nov;106(2):173-81. doi: 10.1016/j.diabres.2014.08.009. Epub 2014 Aug 19.
Abstract
The ketone body β-hydroxybutyrate (βOHB) is a convenient carrier of energy from adipocytes to peripheral tissues during fasting or exercise. However, βOHB is more than just a metabolite, having important cellular signaling roles as well. βOHB is an endogenous inhibitor of histone deacetylases (HDACs) and a ligand for at least two cell surface receptors. In addition, the downstream products of βOHB metabolism including acetyl-CoA, succinyl-CoA, and NAD+ (nicotinamide adenine dinucleotide) themselves have signaling activities. These regulatory functions of βOHB serve to link the outside environment to cellular function and gene expression, and have important implications for the pathogenesis and treatment of metabolic diseases including type 2 diabetes.
摘要
酮体β-羟基丁酸酯（βOHB）是禁食或运动期间脂肪细胞向周围组织输送能量的便捷载体。然而，βOHB不仅仅是一种代谢物，它还具有重要的细胞信号传导作用。βOHB是组蛋白脱乙酰基酶（HDACs）的内源性抑制剂，也是至少两种细胞表面受体的配体。此外，βOHB代谢的下游产物，包括乙酰辅酶A、琥珀酰辅酶A和NAD+（烟酰胺腺嘌呤二核苷酸）本身也具有信号传导活性。βOHB的这些调节功能有助于将外部环境与细胞功能和基因表达联系起来，对包括2型糖尿病在内的代谢性疾病的发病机制和治疗具有重要意义。
相似文献
1
β-hydroxybutyrate: much more than a metabolite.β-羟基丁酸：远不止是一种代谢产物。
Diabetes Res Clin Pract. 2014 Nov;106(2):173-81. doi: 10.1016/j.diabres.2014.08.009. Epub 2014 Aug 19.
2
Ketone bodies as signaling metabolites.酮体作为信号代谢物。
Trends Endocrinol Metab. 2014 Jan;25(1):42-52. doi: 10.1016/j.tem.2013.09.002. Epub 2013 Oct 18.
3
Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor.β-羟丁酸抑制氧化应激，β-羟丁酸是一种内源性组蛋白去乙酰化酶抑制剂。
Science. 2013 Jan 11;339(6116):211-4. doi: 10.1126/science.1227166. Epub 2012 Dec 6.
4
β-Hydroxybutyrate enhances the cytotoxic effect of cisplatin via the inhibition of HDAC/survivin axis in human hepatocellular carcinoma cells.β-羟基丁酸通过抑制 HDAC/survivin 轴增强顺铂对人肝癌细胞的细胞毒性作用。
J Pharmacol Sci. 2020 Jan;142(1):1-8. doi: 10.1016/j.jphs.2019.10.007. Epub 2019 Nov 5.
5
The Ketone Metabolite β-Hydroxybutyrate Attenuates Oxidative Stress in Spinal Cord Injury by Suppression of Class I Histone Deacetylases.酮体代谢物β-羟丁酸通过抑制 class I 组蛋白去乙酰化酶减轻脊髓损伤中的氧化应激。
J Neurotrauma. 2017 Sep 15;34(18):2645-2655. doi: 10.1089/neu.2017.5192. Epub 2017 Aug 4.
6
β-Hydroxybutyrate elevation as a compensatory response against oxidative stress in cardiomyocytes.β-羟基丁酸水平升高作为心肌细胞对氧化应激的一种代偿反应。
Biochem Biophys Res Commun. 2016 Jul 8;475(4):322-8. doi: 10.1016/j.bbrc.2016.05.097. Epub 2016 May 20.
7
RNA sequencing reveals niche gene expression effects of beta-hydroxybutyrate in primary myotubes.RNA 测序揭示了β-羟丁酸对原代肌管中龛基因表达的影响。
Life Sci Alliance. 2021 Aug 18;4(10). doi: 10.26508/lsa.202101037. Print 2021 Oct.
8
β-Hydroxybutyrate, a ketone body, reduces the cytotoxic effect of cisplatin via activation of HDAC5 in human renal cortical epithelial cells.β-羟丁酸，一种酮体，通过激活人肾皮质上皮细胞中的 HDAC5 来降低顺铂的细胞毒性作用。
Life Sci. 2019 Apr 1;222:125-132. doi: 10.1016/j.lfs.2019.03.008. Epub 2019 Mar 6.
9
β-Hydroxybutyrate: A Signaling Metabolite.β-羟基丁酸：一种信号代谢物。
Annu Rev Nutr. 2017 Aug 21;37:51-76. doi: 10.1146/annurev-nutr-071816-064916.
10
β-Hydroxybutyrate in the Brain: One Molecule, Multiple Mechanisms.大脑中的β-羟基丁酸：一种分子，多种机制。
Neurochem Res. 2017 Jan;42(1):35-49. doi: 10.1007/s11064-016-2099-2. Epub 2016 Nov 8.
引用本文的文献
1
Ketogenic Metabolism in Neurodegenerative Diseases: Mechanisms of Action and Therapeutic Potential.神经退行性疾病中的生酮代谢：作用机制与治疗潜力
Metabolites. 2025 Jul 31;15(8):508. doi: 10.3390/metabo15080508.
2
Ketone body β-hydroxybutyrate-mediated histone β-hydroxybutyrylation upregulates lipolysis and attenuates metabolic syndrome.酮体β-羟基丁酸介导的组蛋白β-羟基丁酰化上调脂肪分解并减轻代谢综合征。
Am J Physiol Cell Physiol. 2025 Sep 1;329(3):C726-C743. doi: 10.1152/ajpcell.00453.2025. Epub 2025 Jul 28.
3
Unleashing the potential of exercise: conquering cardiovascular disease by targeting inflammasome activation.释放运动的潜力：通过靶向炎性小体激活来战胜心血管疾病。
Eur J Med Res. 2025 Jul 26;30(1):677. doi: 10.1186/s40001-025-02927-3.
4
Obesity, Dietary Patterns, and Cardiovascular Disease: A Narrative Review of Metabolic and Molecular Pathways.肥胖、饮食模式与心血管疾病：代谢和分子途径的叙述性综述
Curr Issues Mol Biol. 2025 Jun 10;47(6):440. doi: 10.3390/cimb47060440.
5
Acidosis Licenses the NLRP3 Inflammasome-Inhibiting Effects of Beta-Hydroxybutyrate and Short-Chain Carboxylic Acids.酸中毒使β-羟基丁酸酯和短链羧酸具有抑制NLRP3炎性小体的作用。
bioRxiv. 2025 May 7:2025.05.01.650510. doi: 10.1101/2025.05.01.650510.
6
A Comprehensive Perspective on the Biological Effects of Intermittent Fasting and Periodic Short-Term Fasting: A Promising Strategy for Optimizing Metabolic Health.间歇性禁食和周期性短期禁食的生物学效应综合视角：优化代谢健康的一项前景策略。
Nutrients. 2025 Jun 20;17(13):2061. doi: 10.3390/nu17132061.
7
Palmitic Acid Induces Dynamic Time-Dependent Alterations in HDACs, Neuronal Chromatin Acetylation, and Gene Expression.棕榈酸诱导组蛋白去乙酰化酶、神经元染色质乙酰化和基因表达的动态时间依赖性改变。
Neurochem Res. 2025 Jun 30;50(4):220. doi: 10.1007/s11064-025-04469-w.
8
Epigenetic regulators in cancer therapy and progression.癌症治疗与进展中的表观遗传调控因子
NPJ Precis Oncol. 2025 Jun 28;9(1):206. doi: 10.1038/s41698-025-01003-7.
9
Interaction Between Rumen Microbiota and Epithelial Mitochondrial Dynamics in Tibetan Sheep: Elucidating the Mechanism of Rumen Epithelial Energy Metabolism.藏绵羊瘤胃微生物群与上皮线粒体动力学之间的相互作用：阐明瘤胃上皮能量代谢机制
BioTech (Basel). 2025 Jun 5;14(2):43. doi: 10.3390/biotech14020043.
10
Cardiac intermediary metabolism in heart failure: substrate use, signalling roles and therapeutic targets.心力衰竭中的心脏中间代谢：底物利用、信号作用及治疗靶点。
Nat Rev Cardiol. 2025 Jun 22. doi: 10.1038/s41569-025-01166-7.
本文引用的文献
1
NAD+ and sirtuins in aging and disease.衰老与疾病中的烟酰胺腺嘌呤二核苷酸（NAD+）和沉默调节蛋白
Trends Cell Biol. 2014 Aug;24(8):464-71. doi: 10.1016/j.tcb.2014.04.002. Epub 2014 Apr 29.
2
Diabetes: a 21st century challenge.糖尿病：21 世纪的挑战。
Lancet Diabetes Endocrinol. 2014 Jan;2(1):56-64. doi: 10.1016/S2213-8587(13)70112-8. Epub 2013 Dec 3.
3
SIRT5 regulates the mitochondrial lysine succinylome and metabolic networks.SIRT5 调节线粒体赖氨酸琥珀酰化组和代谢网络。
Cell Metab. 2013 Dec 3;18(6):920-33. doi: 10.1016/j.cmet.2013.11.013.
4
β-Hydroxybutyrate modulates N-type calcium channels in rat sympathetic neurons by acting as an agonist for the G-protein-coupled receptor FFA3.β-羟丁酸通过作为 G 蛋白偶联受体 FFA3 的激动剂调节大鼠交感神经元中的 N 型钙通道。
J Neurosci. 2013 Dec 4;33(49):19314-25. doi: 10.1523/JNEUROSCI.3102-13.2013.
5
The nexus of chromatin regulation and intermediary metabolism.染色质调控与中间代谢的联系。
Nature. 2013 Oct 24;502(7472):489-98. doi: 10.1038/nature12752.
6
Ketone bodies as signaling metabolites.酮体作为信号代谢物。
Trends Endocrinol Metab. 2014 Jan;25(1):42-52. doi: 10.1016/j.tem.2013.09.002. Epub 2013 Oct 18.
7
Three single nucleotide variants of the HDAC gene are associated with type 2 diabetes mellitus in a Chinese population: a community-based case-control study.三个 HDAC 基因的单核苷酸变异与中国人群 2 型糖尿病相关：一项基于社区的病例对照研究。
Gene. 2014 Jan 1;533(1):427-33. doi: 10.1016/j.gene.2013.09.123. Epub 2013 Oct 10.
8
Lysine succinylation is a frequently occurring modification in prokaryotes and eukaryotes and extensively overlaps with acetylation.赖氨酸琥珀酰化是原核生物和真核生物中一种常见的修饰方式，并且与乙酰化广泛重叠。
Cell Rep. 2013 Aug 29;4(4):842-51. doi: 10.1016/j.celrep.2013.07.024. Epub 2013 Aug 15.
9
The role of HCA2 (GPR109A) in regulating macrophage function.HCA2（GPR109A）在调节巨噬细胞功能中的作用。
FASEB J. 2013 Nov;27(11):4366-74. doi: 10.1096/fj.12-223933. Epub 2013 Jul 23.
10
Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets.超越减肥：极低碳水化合物（生酮）饮食的治疗用途综述。
Eur J Clin Nutr. 2013 Aug;67(8):789-96. doi: 10.1038/ejcn.2013.116. Epub 2013 Jun 26.
Zotero 插件