Hepatic nuclear receptor networks controlling responses to nutritional challenges – Hepatologic

The liver orchestrates metabolic response to fasting through potent transcriptional regulations. Peroxisome Proliferator-Activated Receptor alpha (PPARa) and the Glucocorticoid Receptor (GR) are pivotal transcription factors in these adaptive processes. They control a network of genes, including Retinol Saturase (RetSat) and Fibroblast Growth Factor 21 (FGF21), to ensure systemic energy homeostasis. Our project is divided in 3 aims: Aim 1 applies unbiased genomic approaches to define the molecular cross-talk between PPARa and GR during fasting and diet-induced obesity; Aim 2 targets the contributions of hepatocyte RetSat and Fgf21 to these metabolic responses. Aim 3 investigates the functional role of these receptors and transcriptional targets in the beneficial effects of time-restricted feeding for diet-induced metabolic diseases. Our project will generate mechanistic insights into the response to fasting and its potential as a target for the treatment of metabolic diseases.