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

Radiana Dhewayani Antarianto, Marcello Mikhael Kadharusman, Shefilyn Wijaya, Novi Silvia Hardiny

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Liver stemness refers to the high regenerative capacity of the organ. This intrinsic regeneration capacity allows the restoration of post-resection liver function in up to 50% of liver donors. Liver cirrhosis is one of the terminal liver diseases with a defect in the intrinsic regeneration capacity. Several attempts to restore intrinsic regeneration capacity by conducting in vi-vo studies on stem cells in various organs have shown the positive impact of fasting on stemness. An increased capacity for stem cell proliferation and regeneration was reported due to fasting. Prolonged fasting (PF) has been reported to maintain the long-term proliferative ability of hematopoi-etic 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 pe-roxisome 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: A total of 18 rabbits were conditioned into 3 different groups. The first group was sub-jected to an ad libitum diet, the second to intermittent fasting (16-hour fasting), and the 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: Compared to the ad libitum diet, a greater increase was reported in PGC-1α, upregulated Oct4, and steady CK-19 gene expressions in the livers of intermittent fasting rabbits. Prolonged fasting increased PGC1α, reduced liver stemness, and a statistically insignificant decrease in intrinsic liver regenerative capacity. Conclusion: Intermittent fasting indicates preferable molecular alterations in liver stemness and intrinsic regenerative capacity compared to prolonged fasting.

Original languageEnglish
Pages (from-to)49-55
Number of pages7
JournalCurrent Aging Science
Volume16
Issue number1
DOIs
Publication statusPublished - Mar 2023

Keywords

  • CK-19
  • fasting
  • Liver
  • Oct-4
  • PGC-1α
  • stemness

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