# Heat stroke-induced hepatic lipid dysregulation: histological and lipidomic insights

## TL;DR

This study explores how heat stroke causes liver damage in mice, revealing lipid accumulation and changes in cholesterol levels that could help diagnose and treat heat stroke.

## Contribution

The study identifies heat stroke-induced hepatic lipid dysregulation and elevated 27-hydroxycholesterol as novel insights into liver injury mechanisms.

## Key findings

- Heat stroke causes lipid accumulation in hepatocytes surrounding the central vein.
- 27-hydroxycholesterol levels significantly increase 24 hours post-heat exposure.
- Lipid accumulation may mediate inflammation and act as a protective response.

## Abstract

Global warming has increased summer temperatures, leading to a rise in heat stroke-related deaths in Japan. Heat stroke disrupts the body's adaptation to high temperatures, often resulting in severe complications, including liver damage and even death. However, despite the increasing incidence, pathological autopsies remain rare, and the histological changes associated with heat stroke are poorly understood. In this study, we investigated the pathogenesis of heat stroke using a mouse model. Mice were exposed to 45 °C for 30 min and dissected immediately or 24, 48, and 72 h post-exposure. Histological analysis revealed significant lipid accumulation in hepatocytes surrounding the central vein at 24, 48, and 72 h. At 24 h, hepatocytes also exhibited features of early degeneration, including cytoplasmic lysis and chromatin condensation. Lipidomics analysis of liver tissue collected 24 h post-exposure demonstrated a marked increase in 27-hydroxycholesterol levels. These results indicate that heat stress rapidly disrupts hepatic lipid homeostasis, causing cellular damage and metabolic remodeling. The observed lipid accumulation, including elevated 27-hydroxycholesterol, may play dual roles in mediating inflammation and serving as a protective response. Our findings provide new insight into the pathogenesis of heat stroke-induced liver injury and suggest potential molecular targets for early diagnosis and intervention.

The online version contains supplementary material available at 10.1007/s00795-025-00441-3.