Ajay Kumar Mishra, Assistant Professor, Department of Hepatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raibareilly Road, Lucknow 226014, Uttar Pradesh, India. ajaymishrapandit@gmail.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Shaiphali Sharma, Department of Physiology, King George Medical College, Lucknow 226014, Uttar Pradesh, India
Shreya Pandey, Ajay Kumar Mishra, Department of Hepatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
Co-first authors: Shaiphali Sharma and Shreya Pandey.
Author contributions: Sharma S and Pandey S have played important roles in manuscript preparation as co-first authors; Mishra AK wrote manuscript; all of the authors read and approved the final version of the manuscript to be published.
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ajay Kumar Mishra, Assistant Professor, Department of Hepatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raibareilly Road, Lucknow 226014, Uttar Pradesh, India. ajaymishrapandit@gmail.com
Received: August 4, 2025 Revised: September 26, 2025 Accepted: December 12, 2025 Published online: March 5, 2026 Processing time: 195 Days and 9.8 Hours
Abstract
The mammalian circadian system comprises of a central clock in the suprachiasmatic nucleus (SCN) and peripheral clocks in body tissues and organs i.e. liver clock. Both the central and liver clocks are based on clock genes and their protein products, which regulate circadian rhythms in metabolism, physiology, and behavior by modulating nervous and harmone signaling, including the sympathetic nervous system, fasting and eating behavior. The SCN is primarily entrained by light-dark cycles. Liver clock genes can be influenced by other factors, such as feeding cycles and specific nutrients. Light is the major entraining factor, reaching the SCN through the retina and retinal hypothalamic tract. The liver clock regulates the expression of 10%-15% of the transcriptome, including key metabolic genes. Disruptions in either the central or liver clock can lead to various health issues, including an increased cancer risk and metabolic disorders. Various lifestyle measures, including time-restricted eating, light therapy, temperature control, and melatonin agonists, have been studied for circadian realignment. We reviewed the mechanism of malalignment of central and liver clock genes and existing therapeutic measures for realignment.
Core Tip: Liver clock is peripheral clock of hepatocytes concerned with metabolic genes and functions. It is desynchronised to central clock in metabolic and life style disorders. It can be resynchronised by various life style and therapeutic measures including modifying eating behaviours, light exposure, excercise or activity modification. This mini-review discusses causes of misalignment of liver clock and how to fix them.
