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Updated: Jul 28, 2025
Measuring Diurnal Rhythms in Autophagic and Proteasomal Flux
Published on: September 17, 2019
Nonalcoholic Steatohepatitis Disrupts Diurnal Liver Transcriptome Rhythms in Mice
Leonardo Vinicius Monteiro de Assis1, Münevver Demir2, Henrik Oster1
1Institute of Neurobiology, Center of Brain Behavior and Metabolism, University of Lübeck, Lübeck, Germany.
Background & Aims:
The liver ensures organismal homeostasis through modulation of physiological functions over the course of the day. How liver diseases such as nonalcoholic steatohepatitis (NASH) affect daily transcriptome rhythms in the liver remains elusive.
Methods:
To start closing this gap, we evaluated the impact of NASH on the diurnal regulation of the liver transcriptome in mice. In addition, we investigated how stringent consideration of circadian rhythmicity affects the outcomes of NASH transcriptome analyses.
Results:
Comparative rhythm analysis of the liver transcriptome from diet-induced NASH and control mice showed an almost 3-hour phase advance in global gene expression rhythms. Rhythmically expressed genes associated with DNA repair and cell-cycle regulation showed increased overall expression and circadian amplitude. In contrast, lipid and glucose metabolism-associated genes showed loss of circadian amplitude, reduced overall expression, and phase advances in NASH livers. Comparison of NASH-induced liver transcriptome responses between published studies showed little overlap (12%) in differentially expressed genes (DEGs). However, by controlling for sampling time and using circadian analytical tools, a 7-fold increase in DEG detection was achieved compared with methods without time control.
Conclusions:
NASH had a strong effect on circadian liver transcriptome rhythms with phase- and amplitude-specific effects for key metabolic and cell repair pathways, respectively. Accounting for circadian rhythms in NASH transcriptome studies markedly improves DEG detection and enhances reproducibility.
