The Circadian Clock and Liver Function in Health and Disease
All organisms are subjected each day to changes in the light intensity generated by the Earth's rotation around its own axis. To anticipate this geo-physical variability, and to appropriately respond biochemically, most species, including mammals, have evolved an approximate 24-hour endogenous timing mechanism known as the circadian clock (CC). The 'clock' is self-sustained, cell autonomous and present in every cell type. At the core of the clock resides the CC-oscillator, an exquisitely crafted transcriptional-translational feedback system. Remarkably, components of the CC-oscillator not only maintain daily rhythmicity of their own synthesis, but also generate temporal variability in the expression levels of numerous target genes through transcriptional, post-transcriptional and post-translational mechanisms, thus, ensuring proper chronological coordination in the functioning of cells, tissues and organs, including the liver. Indeed, a variety of physiologically critical hepatic functions and cellular processes are CC-controlled. It is not surprising then, that the modern lifestyle (e.g. travel and jet lag, night and rotating shift work), which force 'circadian misalignment' have emerged as major contributors to global health problems including obesity, non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH). Here, we provide an overview of the CC-dependent pathways which play critical roles in mediating several hepatic functions under physiological conditions and, whose deregulations are implicated in chronic liver disease including NASH and alcoholic liver disease (ALD).
J Hepatol. 2019 Mar 28. pii: S0168-8278(19)30191-6. doi: 10.1016/j.jhep.2019.03.020. [Epub ahead of print]
Institut de Recherche sur les Maladies Virales et Hépatiques INSERM, UMR 1110, Université de Strasbourg Strasbourg, France. Electronic address: email@example.com.
Department of Pathology, School of Medicine, University of Alabama at Birmingham, USA.
Université de Lille-European Genomic Institute for Diabetes, Institut Pasteur de Lille, CHU de Lille, INSERM UMR 1011, Lille, France.
Institut de Recherche sur les Maladies Virales et Hépatiques INSERM, UMR 1110, Université de Strasbourg Strasbourg, France; Pôle Hépato-Digestif, Institut Hospitalo-Universitaire, Hôpitaux Universitaires de Strasbourg, Strasbourg, France. Electronic address: firstname.lastname@example.org.