Epigenetic regulation of FGF21 signaling in adipose tissue and brain

Project Description:

Adipose tissue secretes multiple factors including adipokines that facilitate the adipocyte-brain-crosstalk and provide feedback about current energy stores. Production and release of adipokines is therefore coupled to overall fat mass and other nutritional cues sensed by the adipose tissue. For instance, obese subjects have elevated circulating levels of the adipokine leptin, commensurate with their adipose mass. Production of adipokines is regulated by hormones including insulin and transcriptional activators. However, the molecular mechanisms of their transcriptional regulation are not fully resolved yet. Recent studies from us and others suggest that the transcription of fibroblast growth factor 21 (FGF21), adiponectin and other adopokines might be regulated by DNA methylation. Nevertheless, systematic studies of epigenetic regulation of adipokine production in various states of obesity and insulin resistance are lacking. Thus, it is currently not clear if the observed alterations in DNA methylation of adipokine genes are causal for obesity or if they are simply a consequence of obesity. This project aims to answer this question using longitudinal mouse studies. Moreover, we aim to reverse the alterations in adipokine methylation using pharmacological and surgical treatment.