Hypothermia drives fatty acid transporter 1 upregulation and lipid accumulation in renal tubules: evidence from forensic cases

Forensic pathology lacks generally accepted markers for hypothermia, relying instead on various physiological responses to low temperatures as postmortem diagnostic indicators. We have demonstrated that fatty acid transporter 1 (FATP1) is upregulated in renal tubules of a mouse hypothermia model, causing lipid accumulation. This study aims to determine if a similar phenomenon occurs in cases of human hypothermia and evaluate its potential as a diagnostic tool. Blood and renal tissue samples were collected from 17 hypothermia cases and 23 non-hypothermia cases. Free fatty acid (FFA) and triglyceride levels were quantified in both blood and renal tissue, while mRNA and protein were extracted from renal tissue to assess FATP1 expression. Oil Red O staining revealed lipid-positive droplets in renal tubular cells in hypothermia cases. Both FFA and triglyceride levels were significantly elevated in the blood and renal tissue samples of hypothermia cases. In cultured human renal tubular cells, low temperature upregulated FATP1 expression and FFA uptake, while FATP1 inhibition reduced FFA uptake. FATP1 mRNA and protein expression were significantly increased in hypothermic renal tissue compared with those in controls. Additionally, this expression positively correlated with FFA content in hypothermic renal tissue. These findings suggest that FATP1-dependent lipid accumulation in renal tubules is a conserved response in both animal models and human hypothermia cases, highlighting its potential as a diagnostic marker in forensic investigations of fatal hypothermia.