FATP1-mediated fatty acid uptake in renal tubular cells as a countermeasure for hypothermia
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 (2025-03-05)
Springer
05.03.2025
Horioka, K., Tanaka, H., Watanabe, S. et al. FATP1-mediated fatty acid uptake in renal tubular cells as a countermeasure for hypothermia. J Mol Med 103, 403–419 (2025). https://doi.org/10.1007/s00109-025-02525-0
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© The Author(s) 2025. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
https://creativecommons.org/licenses/by/4.0/
© The Author(s) 2025. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
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Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:oulu-202503111945
https://urn.fi/URN:NBN:fi:oulu-202503111945
Tiivistelmä
Abstract
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.
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.
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