Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
Front Endocrinol (Lausanne). 2022 Oct 20;13:989305. doi: 10.3389/fendo.2022.989305. eCollection 2022.
Histone deacetylase 11 (HDAC11) is the only member of the class IV HDAC, and the latest member identified. It is highly expressed in brain, heart, kidney and some other organs, and located in mitochondria, cytoplasm and nuclei, depending on the tissue and cell types. Although studies in HDAC11 total knockout mice suggest its dispensable features for tissue development and life, it participates in diverse pathophysiological processes, such as DNA replication, tumor growth, immune regulation, oxidant stress injury and neurological function of cocaine. Recent studies have shown that HDAC11 is also critically involved in the pathogenesis of some metabolic diseases, including obesity, diabetes and complications of diabetes. In this review, we summarize the recent progress on the role and mechanism of HDAC11 in the regulation of metabolic disorders, with the focus on its regulation on adipogenesis, lipid metabolism, metabolic inflammation, glucose tolerance, immune responses and energy consumption. We also discuss the property and selectivity of HDAC11 inhibitors and their applications in a variety of and models of metabolic disorders. Given that pharmacological and genetic inhibition of HDAC11 exerts a beneficial effect on various metabolic disorders, HDAC11 may be a potential therapeutic target to treat chronic metabolic diseases.
组蛋白去乙酰化酶 11（HDAC11）是唯一的 IV 类 HDAC 成员，也是最新发现的成员。它在脑、心、肾和其他一些器官中高度表达，并且根据组织和细胞类型，位于线粒体、细胞质和细胞核中。尽管在 HDAC11 基因敲除小鼠中的研究表明其对于组织发育和生命不是必需的，但它参与了多种病理生理过程，如 DNA 复制、肿瘤生长、免疫调节、氧化应激损伤和可卡因的神经功能。最近的研究表明，HDAC11 还在一些代谢性疾病的发病机制中起着关键作用，包括肥胖、糖尿病和糖尿病并发症。在这篇综述中，我们总结了 HDAC11 在调节代谢紊乱中的作用和机制的最新进展，重点介绍了其对脂肪生成、脂质代谢、代谢炎症、葡萄糖耐量、免疫反应和能量消耗的调节作用。我们还讨论了 HDAC11 抑制剂的特性和选择性及其在各种代谢紊乱模型中的应用。鉴于 HDAC11 的药理学和遗传学抑制对各种代谢紊乱都有有益的作用，HDAC11 可能是治疗慢性代谢性疾病的潜在治疗靶点。
