Submitted by Sona Kang on
Obesity is a grave health threat. Despite extensive research and investment around the world, it remains highly challenging to overcome. The cause of obesity involves the complex interaction between gene–environment, which is mediated by epigenetic mechanisms. DNA methylation is a major epigenetic modification and we and others have demonstrate that it plays an important role in multiple aspects of adipose tissue development and function. Ten-eleventranslocation (TET) proteins are methylcytosine oxygenase and act as active DNA demethylase. Some studies have suggested that TETs may play a role in regulating in vitro adipogenesis. However, it remains unknown whether and how they regulate adipose development in vivo and what impact it has on whole body metabolism.
The goal of this proposal is to better understand how epigenetics regulates adipose tissue development and remodeling during chronic nutrition and determine the metabolic impacts. Our preliminary studies have discovered that TET3 expression is induced during in vitro and in vivo adipogenesis. Tet3 deficiency in vitro inhibited adipogenesis in cultured adipocyte models. In line with this, ablation of Tet3 in PDGFRa-positive adipocyte precursor cells (APCs) led to reduced white adipose development. PDGFRa-Tet3 KO mice did not display any discernable metabolic changes when reared on a regular chow diet. However, when put on a high fat diet, the KO mice were highly resistant to diet induced obesity (DIO) with a dramatic improvement of metabolic profiles. Based upon these novel preliminary findings, we hypothesize that TET3 is a key epigenetic regulator of adipose tissue expansion and metabolism by regulating critical target genes in APCs and cell fate during diet-induced obesity. To test that, we will assess adipogenic potential of PDGFRa+ WT and KO APCs by culturing them to adipogenesis and by performing transplanting them into WT and KO niches. We have identified a set of key target genes of TET3 in APCs. In the next cycle, we will focus on studying the functional role of TET3 target genes in adipogenesis and adipose remodeling in vitro and in vivo.
Learn basic lab techniques (e.g., western blotting, RNA-extraction, etc.), attend lab meetings.
We look for students who are mature and who can dedicate a significant effort to research.