Horioka Kie, Tanaka Hiroki, Watanabe Shimpei, Yamada Shinnosuke, Takauji Shuhei, Hayakawa Akira, Isozaki Shotaro, Okaba Keisuke, Ishii Namiko, Motomura Ayumi, Inoue Hiroyuki, Addo Lynda, Yajima Daisuke, Takahashi Yoichiro, Druid Henrik, Pakanen Lasse, Porvari Katja
Department of Forensic Medicine, Research Unit of Biomedicine and Internal Medicine, Medical Research Center Oulu, University of Oulu, Oulu, Finland.
Department of Legal Medicine, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
J Mol Med (Berl). 2025 Apr;103(4):403-419. doi: 10.1007/s00109-025-02525-0. Epub 2025 Mar 5.
Hypothermia is a condition in which body temperature falls below 35 °C, resulting from exposure to low environmental temperatures or underlying medical conditions. Postmortem examinations have revealed increased levels of fatty acids in blood and lipid droplet formation in renal tubules during hypothermia. However, the causes and implications of these findings are unclear. This study aimed to analyze the biological significance of these phenomena through lipidomics and transcriptomics analyses of specimens from emergency hypothermia patients and mouse hypothermia models. Both human hypothermia patients and murine models exhibited elevated plasma concentrations of fatty acids and their derivatives compared with controls. Hypothermic mouse kidneys displayed lipid droplet formation, with gene expression analysis revealing enhanced fatty acid uptake and β-oxidation in renal tubular cells. In primary cultured mouse renal proximal tubular cells, low temperatures increased the expression levels of Fatty acid transport protein 1 (FATP1), a fatty acid transporter, and boosted oxygen consumption via β-oxidation. Mice treated with FATP1 inhibitors showed a more rapid decrease in body temperature upon exposure to low temperatures compared with untreated mice. In conclusion, increased fatty acid uptake mediated by FATP1 in renal tubular cells plays a protective role during hypothermia. KEY MESSAGES: Low temperatures increase FATP1 expression and fatty acid uptake in renal proximal tubular cells, resulting in enhanced β-oxidation. Renal proximal tubular cells play an important role in the resistance to hypothermia via lipid uptake. Maintaining renal lipid metabolism is essential for cold stress adaptation.
体温过低是指体温降至35°C以下的一种情况，其由暴露于低环境温度或潜在的医疗状况引起。尸检显示，体温过低期间血液中脂肪酸水平升高，肾小管中出现脂滴形成。然而，这些发现的原因和影响尚不清楚。本研究旨在通过对急诊体温过低患者和小鼠体温过低模型的标本进行脂质组学和转录组学分析，来分析这些现象的生物学意义。与对照组相比，人类体温过低患者和小鼠模型的血浆中脂肪酸及其衍生物的浓度均升高。体温过低的小鼠肾脏出现脂滴形成，基因表达分析显示肾小管细胞中脂肪酸摄取和β-氧化增强。在原代培养的小鼠肾近端小管细胞中，低温增加了脂肪酸转运蛋白1（FATP1）（一种脂肪酸转运体）的表达水平，并通过β-氧化增加了氧气消耗。与未处理的小鼠相比，用FATP1抑制剂处理的小鼠在暴露于低温时体温下降更快。总之，肾小管细胞中由FATP1介导的脂肪酸摄取增加在体温过低期间起保护作用。关键信息：低温增加肾近端小管细胞中FATP1的表达和脂肪酸摄取，导致β-氧化增强。肾近端小管细胞通过脂质摄取在抵抗体温过低中起重要作用。维持肾脏脂质代谢对于冷应激适应至关重要。
