Distinct Roles of Two Types of Lipid Droplets inside the Nucleus in Liver Diseases

Aim: Lipid droplets have been found in the nuclei of hepatocytes, however, their role in liver is not clearly understood. The purpose of this study was to explore the pathophysiological roles of intranuclear lipid droplets in liver diseases. Method This study included 80 patients who underwent liver biopsies. A part of the liver biopsy specimen was dissected and fixed for electron microscopic observation. Lipid droplets in the nuclei were distinguished into two types based on the presence of adjacent cytoplasmic invagination of the nuclear membrane: nuclear lipid droplet (nLD) and cytoplasmic lipid droplet invagination with nucleoplasmic reticulum (cLD in NR). Results nLDs were found in 69% of the liver biopsy samples, and cLDs in NR were found in 32%. A significant positive correlation was observed between the frequencies of nLD and cLD in NR. Although nLD was frequently found in hepatocytes of patients with nonalcoholic steatohepatitis, there was no correlation between the frequency of nLD and hepatic steatosis, indicating that nLD does not directly reflect cytoplasmic lipid accumulation. Significant positive correlations were found between the frequencies of nLD and endoplasmic reticulum (ER) expansion or liver enzymes, suggesting that nLD is formed in the nucleus under ER stress. Conversely, cLD in NR showed a significant negative correlation with hepatic steatosis, implying that cLD in NR is formed in lipid-restricted hepatocytes. Moreover, no correlations were observed between the frequency of cLD in NR and ER expansion. Conclusion This study revealed two distinct pathophysiological roles of lipid droplets in liver diseases.