Changes in the pool of bile acids in hepatocyte nuclei during rat liver regeneration

Background/Aims: To investigate changes in nuclear bile acids (BAs) during rat liver regeneration. Methods: Nuclei were isolated from control rat livers and after two-thirds partial hepatectomy (PH). BAs in bile, liver homogenate and nuclei were measured by gas chromatography–mass spectrometry. Nuclear translocation of radiolabeled BAs was determined using fresh isolated hepatocytes from control donors. Results: Liver BA concentrations were transiently reduced after PH. Relative increases in: β-MCA at 1 day, deoxycholic acid at 7 days and cholic acid (CA) at 3 and 14 days were found. Nuclear BAs accounted for <0.5% of liver BAs. Contamination with cytosolic BAs during nuclei isolation was <4%. Unconjugated- and conjugated-CA were able to reach the nucleus with similar efficiency. The pattern of nuclear BAs – CA (80%) and ursodeoxycholic acid (UDCA) (8.5%) being the most abundant – did not match that found in liver or bile. A transient decrease in CA/UDCA ratio, in absence of significant change in total BA content, was observed in nuclei after PH. ‘Flat’ BA species were only detected in homogenate, but not in nuclei, at 1 day after PH. Conclusions: BA pool in nuclei of rat hepatocytes, whose composition is different to that of total liver BA pool, undergoes important changes during liver regeneration.