Digestive Diseases and Sciences

, Volume 63, Issue 12, pp 3187–3206 | Cite as

Role of the Circadian Clock in the Metabolic Syndrome and Nonalcoholic Fatty Liver Disease

  • Akshay Shetty
  • Jennifer W. Hsu
  • Paul P. Manka
  • Wing-Kin SynEmail author


Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in industrialized nations and is strongly associated with the metabolic syndrome. The prevalence of NAFLD continues to rise along with the epidemic of the metabolic syndrome. Metabolic homeostasis is linked to the circadian clock (rhythm), with multiple signaling pathways in organs regulated by circadian clock genes, and recent studies of circadian clock gene functions suggest that disruption of the circadian rhythm is associated with significant morbidity and mortality, including the metabolic syndrome. In the industrialized world, various human behaviors and activities such as work and eating patterns, jet lag, and sleep deprivation interfere with the circadian rhythm, leading to perturbations in metabolism and development of the metabolic syndrome. In this review, we discuss how disruption of the circadian rhythm is associated with various metabolic conditions that comprise the metabolic syndrome and NAFLD.


Circadian rhythm Fatty liver Nonalcoholic steatohepatitis Obesity Diabetes mellitus 



Figures were created with “Biological illustration” ( by Servier, used under Creative Commons Attribution 3.0 Unported License, and modified by Akshay Shetty and Paul Manka.


Resources were provided by the Ralph H Johnson VAMC, Charleston, South Carolina.

Compliance with ethical standards

Conflict of interest



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© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2018

Authors and Affiliations

  1. 1.Division of Gastroenterology and HepatologyMedical University of South CarolinaCharlestonUSA
  2. 2.Division of Gastroenterology and HepatologyUniversity Hospital EssenEssenGermany
  3. 3.Section of GastroenterologyRalph H Johnson Veterans Affairs Medical CenterCharlestonUSA

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