ORCID

0009-0003-0978-1886 (Slover)

Document Type

Article

Publication Date

2026

DOI

10.14218/JTG.2026.00003

Publication Title

Journal of Translational Gastroenterology

Volume

Advance online publication

Pages

13 pp.

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD), defined by the American Association for the Study of Liver Diseases as hepatic steatosis with at least one cardiometabolic risk factor, affects approximately 30-40% of adults worldwide. This condition may progress to fibrosis, cirrhosis, and hepatocellular carcinoma. The rising prevalence, alongside obesity and type 2 diabetes, underscores the need for early risk stratification and integrated therapeutic strategies. Circadian homeostasis, orchestrated by the suprachiasmatic nucleus and core clock gene feedback loops, synchronizes hepatic metabolic pathways with environmental light-dark cycles. The objective of this review is to evaluate the role of circadian disruption and metabolic dysfunction in the development of hepatic steatosis, as well as to assess current and potential treatment modalities for both disorders. Circadian disruption through shift work, artificial light at night, sleep restriction, and chrono-nutritional misalignment destabilizes hepatic clocks, promoting insulin resistance, dyslipidemia, inflammation, and steatosis. Experimental models demonstrate that clock gene dysfunction alone can induce steatohepatitis, while progressive MASLD further impairs central circadian regulation, establishing a self-reinforcing chrono-metabolic cycle. Pharmacologic therapies, including glucagon-like peptide-1 receptor agonists and thyroid hormone receptor-beta agonists, improve histologic endpoints and fibrosis regression, although heterogeneity among clinical trials precludes direct comparison. Recent evidence characterizing MASLD as a predominantly nocturnal metabolic disorder further highlights persistent nighttime insulin dysregulation despite weight loss, emphasizing the potential role of circadian-targeted interventions such as melatonin. In conclusion, the peripheral circadian clock is intricately linked with MASLD pathogenesis, and metabolic dysfunction, in turn, disrupts circadian pathways. Several pharmacologic therapies offer potential for the treatment of MASLD and circadian dysfunction.

Rights

© 2026 The Authors

This article has been published under the terms of the Creative Commons Attribution-Noncommercial 4.0 International License (CC BY-NC 4.0), which permits noncommercial unrestricted use, distribution, and reproduction in any medium, provided that the following statement is provided: "This article has been published in Journal of Translational Gastroenterology at https://doi.org/10.14218/JTG.2026.00003 and can also be viewed on the Journal's website at https://www.xiahepublishing.com/journal/jtg.

Original Publication Citation

Slover, W. K., Huang, A. V., D'Souza, S. M., Oldfield, E. C., & Johnson, D. A. (2026). Metabolic dysfunction-associated steatotic liver disease and circadian rhythm: Current understanding and implications for future therapeutic interventions. Journal of Translational Gastroenterology. Advance online publication. https://doi.org/10.14218/JTG.2026.00003

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