The Impact of Prolonged and Intermittent Fasting on PGC-1α, Oct-4, and CK-19 Liver Gene Expression

Abstract

Background: Liver stemness refers to the highly regenerative capacity of the organ. This intrinsic regeneration capacity allows the restoration of post-resection liver function in up to 50% of liver donor. Liver cirrhosis is one of the terminal liver diseases with a defect in the intrinsic regeneration capacity. Several attempts to restore intrinsic regeneration capacity from in vivo studies of stem cells in various organs have shown the positive impact of fasting on stemness. There is an increased capacity for stem cell proliferation and regeneration due to fasting. Prolonged fasting (PF) has been reported to maintain the long-term proliferative ability of hematopoietic stem cells. However, clinical trials on intermittent fasting (IF) have not conclusively given positive results for fasting individuals. Objectives: This research aims to investigate the effect of fasting on liver stemness by comparing the expression of octamer-binding transcription factor 4 (Oct-4), cytokeratin 19 (CK-19) and peroxisome proliferator-activated receptor γ co-activator α (PGC-1α) in liver cells of fasted rabbits with rabbits fed ad libitum. This study compares two types of fasting which are intermittent (16 hours) and prolonged (40 hours) fasting for liver stemness and intrinsic regenerative capacity. Methods: 18 rabbits were conditioned into 3 different groups. The first group was subjected to ad libitum diet, second to intermittent fasting (16-hour fasting), and third to prolonged fasting (40-hour fasting). Afterward, the RNA was extracted from the liver tissues of each rabbit and analyzed via real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Relative expression was calculated using the Livak method. Results: In comparison to the ad libitum diet, there were higher increase in PGC-1α, upregulated Oct4 and steady CK-19 gene expressions in the liver of intermittent fasting liver. Prolonged fasting increased PGC1α, reduced liver stemness, and a statistically insignificant decrease of intrinsic liver regenerative capacity. Conclusion: Intermittent fasting indicates preferable molecular alterations in liver stemness and intrinsic regenerative capacity compared to prolonged fasting.