美国宾夕法尼亚大学Mitchell A. Lazar研究团队发现，短期低温暴露诱导褐色脂肪的持久表观基因组记忆。相关论文于2024年6月17日发表在《细胞—代谢》杂志上。

该研究组报道，短期暴露于轻度寒冷温度（STEMCT：15°C，24小时）可防止缺乏棕色脂肪组织中HDAC3的小鼠，（HDAC3 BAT KO）在4°C暴露下发生致命的低体温。在22°C时，STEMCT恢复了热生成辅助因子PGC-1α和UCP1的诱导，这在HDAC3缺失的褐色脂肪组织中严重受损，UCP1或PGC-1α的缺失阻止了STEMCT的保护作用。

值得注意的是，这种保护持续了7天。转录激活因子C/EBPβ在小鼠和人褐色脂肪组织中通过短期冷暴露被诱导，并且在STEMCT后7天内保持高水平。腺相关病毒介导的HDAC3褐色脂肪组织敲除小鼠中，褐色脂肪组织C/EBPβ的敲低消除了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基因组记忆的存在。

据悉，褐色脂肪组织(BAT)中表观基因组调节因子组蛋白去乙酰化酶3 (HDAC3)的缺失，会损害小鼠在接近冰点温度下的生存能力。

附：英文原文

Title: Short-term cold exposure induces persistent epigenomic memory in brown fat

Author: 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

Issue&Volume: 2024-06-17

Abstract: Deficiency of the epigenome modulator histone deacetylase 3 (HDAC3) in brown adiposetissue (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 for24 h) averted lethal hypothermia of mice lacking HDAC3 in BAT (HDAC3 BAT KO) exposedto 4°C. STEMCT restored the induction of the thermogenic coactivator PGC-1α alongwith UCP1 at 22°C, which is greatly impaired in HDAC3-deficient BAT, and deletionof either UCP1 or PGC-1α prevented the protective effect of STEMCT. Remarkably, thisprotection lasted for up to 7 days. Transcriptional activator C/EBPβ was induced byshort-term cold exposure in mouse and human BAT and, uniquely, remained high for 7 daysfollowing STEMCT. Adeno-associated virus-mediated knockdown of BAT C/EBPβ in HDAC3BAT KO mice erased the persistent memory of STEMCT, revealing the existence of a C/EBPβ-dependentand HDAC3-independent cold-adaptive epigenomic memory.

DOI: 10.1016/j.cmet.2024.05.011

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(24)00187-6