FATP1-mediated Fatty Acid Uptake in Renal Tubular Cells As a Countermeasure for Hypothermia

Overview

Journal J Mol Med (Berl)

Specialty General Medicine

Date 2025 Mar 5

PMID 40042587

Authors

Kie Horioka

Hiroki Tanaka

Shimpei Watanabe

Shinnosuke Yamada

Shuhei Takauji

Akira Hayakawa

Shotaro Isozaki

Keisuke Okaba

Namiko Ishii

Ayumi Motomura

Hiroyuki Inoue

Lynda Addo

Daisuke Yajima

Yoichiro Takahashi

Henrik Druid

Lasse Pakanen

Katja Porvari

Affiliations

Soon will be listed here.

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. 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.

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