Uddannelses- og Forskningsministeriet - FNU - Identification of novel mechanisms regulating hepatic transcriptional response to high fat diet reprogramming CREB

Functional genomics approaches are becoming very powerful strategies to identify novel transcriptional signaling pathways in complex regulatory processes such as cell differentiation and cancer development. Diet induced obesity is associated with hepatic transcriptional reprogramming regulated by multiple transcription factors. In the past these processes have mostly been described by relative simple gene-by-gene approaches. This project aims use genome-wide technologies such as DNase-seq, ChIP-seq and RNA-seq to comprehensive identify differentially regulated hepatic transcriptional networks in response to different diet regiments such as a high fat diet (HFD) and calorie restriction.

Specifically this project will identify key regulatory networks in liver important for transcriptional reprogramming in response to different diets. It is expected that this will provide novel insight into potentially drug able pathways for improvement of obesity-associated complications such as insulin resistance and type II diabetes. Importantly, this project will also function as a proof-of-principle study for future functional pathophysiological genomic-based studies in different mouse models and other tissues such as muscle and fat. Future comparative analysis of tissue specific genomic response to HFD will provide insights to tissue specific regulation of insulin signaling and will broaden the understanding of tissue selective metabolic signaling.