Glucocorticoids in circadian metabolic rhythms

• Applicant: Dr. Marjolein Heddes
• Subject Area: Endocrinology, Diabetology, Metabolism
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 560358580

This project focuses on how the timing of food intake affects the interaction between glucocorticoids (GCs) and their receptor (GR) in the liver and its implications for metabolism. Glucocorticoids are hormones that help the body manage stress and play a critical role in regulating metabolic processes. They are released in a daily rhythm, synchronized with the circadian clock, which governs many physiological functions, including metabolism. When the timing of eating is misaligned with this rhythm—such as consuming meals during the body's inactive phase—it may disrupt the natural interaction between GCs and GR, potentially leading to metabolic disorders.The main objective of this research is to understand how meal timing modulates the interaction between glucocorticoids and the GR in the liver and the consequences for overall metabolic regulation. To achieve this, two mouse models will be used: wildtype mice with normal functioning GR and another where the GR is specifically removed from liver cells. These mice will be subjected to feeding schedules that either align with their active phase (nighttime for mice) or disrupt it (daytime feeding). By comparing the metabolic effects of eating during the correct and incorrect times, we aim to uncover how disrupted food timing impacts liver metabolism specifically modulated by GR.To delve into the molecular mechanisms behind these changes, the project will employ advanced techniques like RNA sequencing and chromatin immunoprecipitation sequencing (ChIP-seq) to map out the genes and co-regulators modulated by the glucocorticoid receptor based on feeding times. This will allow us to identify the specific GR target genes that regulate key metabolic pathways, including lipid metabolism, gluconeogenesis, and circadian-related processes.Ultimately, the findings from this research could provide important insights into how eating habits influence liver metabolism and contribute to the development of metabolic diseases such as obesity, diabetes, and non-alcoholic fatty liver disease. This is particularly relevant in today’s society, where irregular eating patterns are common and often linked to metabolic health problems.

• DFG Programme: WBP Position