Cold exposure accelerates lysine catabolism to promote cold acclimation via remodeling hepatic histone crotonylation

作者：Chong Xue, Sijin Zhu, Li Yang, Xiaoming Chen, Lu Liang, Peng Su, Qian Zhang, Xinqin Liu, Ruili Guan, Zongcai Liu, Zhiwei Zhao, Shan Tang, Jingyuan Chen, Jianbin Zhang, Wenbin Zhang, Huanyu Lu, Wenjing Luo · 发表于：Environment International · 年份：2024 · DOI：10.1016/j.envint.2024.109015 · 被引用次数：5 · 研究领域：Adipose Tissue and Metabolism、Thermoregulation and physiological responses、Thermal Regulation in Medicine

BACKGROUND: Cold environments pose serious threats on human health, with increased risk for myocardial infarction, stroke, frostbite, and hypothermia. Acquired cold acclimation is required to minimize cold-induced injures and to improve metabolic health. However, the underlying mechanisms remain to be fully elucidated. OBJECTIVE: We aimed to identify critical amino acids involved in cold acclimation and unmask the regulatory mechanisms. METHODS: A total of twenty male participants were recruited and followed up after 3 months' natural cold exposure. Cold-induced vasodilation (CIVD) tests and clinical biochemical analysis were performed at baseline and after 3-months cold exposure, whilst blood samples were collected, and plasma amino acids were analyzed by targeted metabolomics. To further confirm the effect of lysine on cold tolerance and explain the latent mechanism, mice were challenged with chronic cold exposure for 7 days with lysine supplement, then core and local surface temperature as well as thermogenesis activity were detected. RESULTS: Continuous cold exposure shortened the CIVD onset time and increased the average finger temperature. Levels of the plasma lysine and glycine were decreased in both humans and mice. Venn analysis from three datasets revealed that lysine was the only significantly changed plasma amino acid, which strongly correlated with the altered CIVD. Moreover, mice sustained a relatively higher core temperature and surface temperature in the back,...