{Reference Type}: Journal Article
{Title}: Short-term cold exposure induces persistent epigenomic memory in brown fat.
{Author}: Inoue SI;Emmett MJ;Lim HW;Midha M;Richter HJ;Celwyn IJ;Mehmood R;Chondronikola M;Klein S;Hauck AK;Lazar MA;
{Journal}: Cell Metab
{Volume}: 36
{Issue}: 8
{Year}: 2024 Aug 6
{Factor}: 31.373
{DOI}: 10.1016/j.cmet.2024.05.011
{Abstract}: 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.