Circadian clock genes: Their influence on liver metabolism, disease development and treatment (Review)

📖 Top 30% JournalOct 17, 2025Molecular medicine reports

How Body Clock Genes Affect Liver Metabolism, Disease, and Treatment

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Abstract

Circadian clock genes may significantly influence liver metabolism and disease progression.

Disruption of circadian rhythms is associated with the development of various liver diseases, including non-alcoholic fatty liver disease and hepatocellular carcinoma.
Key circadian regulators, such as circadian locomotor output cycles kaput and brain and muscle ARNT-like protein 1, affect lipid and glucose metabolism, bile acid synthesis, and inflammatory responses.
Chronotherapeutic approaches like targeted pharmacological treatments and time-restricted feeding could offer new strategies for managing liver disease.
Further research is needed to understand the mechanisms involved and to facilitate the clinical application of circadian rhythm-based therapies.

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The present review comprehensively discusses the impact of circadian clock genes on hepatic metabolism, liver disease progression and therapeutic strategies. The circadian rhythm, as a fundamental regulatory system, governs metabolic, immune and endocrine processes through an integrated central‑peripheral network. Disruption of this rhythm plays a pivotal role in the pathogenesis of various liver diseases, including non‑alcoholic fatty liver disease, alcoholic liver disease, liver fibrosis and hepatocellular carcinoma. Key circadian regulators, including circadian locomotor output cycles kaput, brain and muscle ARNT‑like protein 1, period circadian regulator 1/2 and cryptochrome 1/2 modulate critical pathways, including lipid and glucose metabolism, bile acid synthesis, inflammatory responses and cellular repair, thereby contributing to the progression of liver disease. Chronotherapeutic approaches, such as targeted pharmacological treatments, time‑restricted feeding and light therapy, show promising clinical potential. However, further research is essential to clarify the underlying mechanisms and enable clinical application. By integrating foundational studies with clinical evidence, the present review provides a framework for chrono‑precision medicine in hepatology, while identifying current challenges and proposing strategies to accelerate the development and clinical implementation of circadian rhythm‑based therapies for liver disease.

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