Shin-ichi Inoue, Matthew J. Emmett, Hee-Woong Lim, Mohit Midha, Hannah J. Richter, Isaac J. Celwyn, Rashid Mehmood, Maria Chondronikola, Samuel Klein, Amy K. Hauck, Mitchell A. Lazar
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引用次数: 0
摘要
棕色脂肪组织(BAT)中表观基因组调节剂组蛋白去乙酰化酶3(HDAC3)的缺乏会损害小鼠在接近冰点的温度下生存的能力。在这里,我们报告了短期暴露于轻度低温(STEMCT:15°C,持续24小时)可避免BAT中缺乏HDAC3的小鼠(HDAC3 BAT KO)暴露于4°C的致命低体温。STEMCT 恢复了 22°C 下生热辅助激活因子 PGC-1α 和 UCP1 的诱导,而在 HDAC3 缺失的 BAT 中,UCP1 和 PGC-1α 的诱导功能严重受损。值得注意的是,这种保护作用可持续长达 7 天。在小鼠和人类 BAT 中,转录激活因子 C/EBPβ 通过短期寒冷暴露被诱导,并且在 STEMCT 之后的 7 天内一直保持高水平。在 HDAC3 BAT KO 小鼠中,腺相关病毒介导的 BAT C/EBPβ 敲除消除了 STEMCT 的持久记忆,揭示了 C/EBPβ 依赖性和 HDAC3 非依赖性冷适应性表观记忆的存在。
Short-term cold exposure induces persistent epigenomic memory in brown fat
Deficiency of the epigenome modulator histone deacetylase 3 (HDAC3) in brown adipose tissue (BAT) impairs the ability of mice to survive in near-freezing temperatures. Here, we report that short-term exposure to mild cold temperature (STEMCT: 15°C for 24 h) averted lethal hypothermia of mice lacking HDAC3 in BAT (HDAC3 BAT KO) exposed to 4°C. STEMCT restored the induction of the thermogenic coactivator PGC-1α along with UCP1 at 22°C, which is greatly impaired in HDAC3-deficient BAT, and deletion of either UCP1 or PGC-1α prevented the protective effect of STEMCT. Remarkably, this protection lasted for up to 7 days. Transcriptional activator C/EBPβ was induced by short-term cold exposure in mouse and human BAT and, uniquely, remained high for 7 days following STEMCT. Adeno-associated virus-mediated knockdown of BAT C/EBPβ in HDAC3 BAT KO mice erased the persistent memory of STEMCT, revealing the existence of a C/EBPβ-dependent and HDAC3-independent cold-adaptive epigenomic memory.
期刊介绍:
Cell Metabolism is a top research journal established in 2005 that focuses on publishing original and impactful papers in the field of metabolic research.It covers a wide range of topics including diabetes, obesity, cardiovascular biology, aging and stress responses, circadian biology, and many others.
Cell Metabolism aims to contribute to the advancement of metabolic research by providing a platform for the publication and dissemination of high-quality research and thought-provoking articles.