Ruina Wang, Lei Xiao, Jianbo Pan, Guangsen Bao, Yunmei Zhu, Di Zhu, Jun Wang, Chengfeng Pei, Qinfeng Ma, Xian Fu, Ziruoyu Wang, Mengdi Zhu, Guoxiang Wang, Ling Gong, Qiuping Tong, Min Jiang, Junchi Hu, Miao He, Yun Wang, Tiejun Li, Chunmin Liang, Wei Li, Chunmei Xia, Zengxia Li, Dengke K Ma, Minjia Tan, Jun Yan Liu, Wei Jiang, Cheng Luo, Biao Yu, Yongjun Dang
Induction of hypothermia during hibernation/torpor enables certain mammals to survive under extreme environmental conditions. However, pharmacological induction of hypothermia in most mammals remains a huge challenge. Here we show that a natural product P57 promptly induces hypothermia and decreases energy expenditure in mice. Mechanistically, P57 inhibits the kinase activity of pyridoxal kinase (PDXK), a key metabolic enzyme of vitamin B6 catalyzing phosphorylation of pyridoxal (PL), resulting in the accumulation of PL in hypothalamus to cause hypothermia...
September 26, 2023: Nature Communications