The twin epidemics of obesity and tType 2 diabetes have beenare a serious health, social, and economic issues. The dysregulation of adipose tissue biology is central to the development of these two metabolic disorders, as adipose tissueAdipose tissue plays a pivotal role in the regulatingon of whole- body metabolism and energy homeostasis. Hence, dysregulation of adipose tissue biology is central to the development of these two metabolic disorders. Accumulating evidence indicates that multiple aspects of adipose biology are regulated, in part, by epigenetic mechanismss plays an important role in the regulation of multiple aspects of adipose biology. The precise and comprehensive understanding of the epigenetic control of adipose tissue biology is crucial to identifying novel therapeutic interventions by that targeting epigenetic issues.
Our group recently demonstrated that DNA methylation machinery, such as DNA methyltransferase (DNMTs) and DNA demethylase (TETs) affect adipocyte insulin sensitivity both in vitro and in vivo. For example, Adipose Dnmt3a plays a causal role in the development of insulin resistance, as evidenced by that adipose-specific deficiency of Dnmt3a conferring protection from diet-induced metabolic dysregulation inindependent of dissociation with body weight or adiposity.
In obesity, white adipose tissue undergoes pathologic expansion that is characterized by adipocyte hypertrophy, inflammation, and fibrosis; however, factors triggering this maladaptive remodeling are largely unknown.
Our ongoing studies reveal that DNA methylation plays important role in the regulation of adipose tissue remodeling in response to high fat diet feeding.
To pursue this line of research, we put forward following key experiments.
What is the role of DNMT3a in high fat feeding-induced the adipose remodeling in vivo?
We will assess hypertrophy, inflammation, hyperplasia, and fibrosis in adipocyte precursor cell-specific knock-out mice upon high fat feeding. To that end, we will perform histological, molecular, and functional examination of wild type and knock-out adipose tissues from chow vs high fat fed mice.
What is the underlying mechanisms by which DNMT3a regulate the processes?
We will perform DNMT3a localization analysis by chromatin immunoprecipitation analysis to look for the genomic target of DNMT3a as well as DNA methylation analysis.
Undergraduate researchers from SPUR program are expected to participate in various in vivo studies including mouse colony maintenance, weight gain monitoring, insulin and glucose tolerance test, and gene expression analysis.
We are seeking for students who are potentially interested in pursuing graduate program.