Circadian Biology in the Zierath Group

The Zierath Group investigates the interactions between intrinsic biorhythms and external perturbations such as exercise, nutrient availability and temperature to identify potent translational strategies for prevention and treatment of metabolic disease.

Research focus

Physical exercise and diet have both individual and synergistic effects on insulin sensitivity, such that the timing of a meal or distribution of nutrients throughout the day can optimize the metabolic homeostasis. Thus, there is a burgeoning appreciation of circadian rhythmicity of both skeletal muscle and adipose tissue. The precise molecular mechanisms for the health-promoting effects of these interventions are largely unknown.

The overarching objective of the Zierath Group is to elucidate the interactions between intrinsic biorhythms and external perturbations for example, exercise, nutrient availability and temperature to identify potent translational strategies for prevention and treatment of metabolic disease. We study how oscillations in epigenetic modifications, gene expression, protein levels, and metabolite concentrations are integrated to cumulatively create tissue-specific physiological biorhythms. We also investigate how this regulatory framework responds and adapts to physical activity and diet. Finally, we work to determine whether the beneficial effect of exercise on metabolism is dependent on internal peripheral clocks and translate these discoveries into innovative exercise intervention strategies to improve insulin sensitivity.

Main findings

“Integrative biology of exercise”
Published in Cell in 2014 this article provides a comprehensive overview of the multiplicity and complexity of cellular networks involved in exercise responses.

”Altered DNA methylation of glycolytic and lipogenic genes in liver from obese and type 2 diabetic patients”
Published in Molecular Metabolism in 2016 this study investigates how epigenetic modifications contribute to the etiology of type 2 diabetes and finds that obesity appears to shift the epigenome to increase lipid production and insulin resistance.

“Acute exercise remodels promoter methylation in human skeletal muscle”
Published in Cell Metabolism in 2012 this study examines the role DNA methylation plays in exercise-induced gene expression and shows that acute gene activation is associated with a dynamic change in DNA methylation in skeletal muscle and suggest that DNA hypomethylation is an early event in contraction-induced gene activation.

Staff of the Zierath Group

Group Leader: Executive Director Juleen R. Zierath

The Zierath Group