Submitted by Sona Kang on
Previously, our lab demonstrated that adipocyte-specific Dnmt3a deficient mice display improved insulin sensitivity and glucose intolerance on high fat-fed condition. Our follow-up transcriptomic studies identified gene X as a top-induced gene in the epididymal white adipose tissue (WAT) compared to controls. We have gathered compelling and exciting preliminary data supporting the hypothesis that the protein product encoded from gene X functions as an adipocyte-derived secretory factor that mediates anti-inflammation and enhances insulin sensitivity. We have found that Protein X expression is enriched in adipocytes compared to stromal vascular fraction of cells, which contains various non-adipocyte cell types such as preadipocytes and immune cells. Protein X expression in adipocytes markedly decreases in obesity. Also importantly, the levels of secreted protein X in serum and the conditioned media from WAT explants dramatically reduced in diet-induced obese mice. Our gain- and loss-of-function studies suggest that protein X plays a protective role in inflammation-mediated insulin resistance. Additionally, protein X effectively suppressed inflammation by inhibiting the activation of proinflammatory cytokine genes. The goal of this proposal is to determine underlying mechanisms through which protein X promotes insulin sensitivity and evaluate its therapeutic efficacy in insulin resistance.
Aim 1. Determine how protein X expression and secretion are regulated in obesity.
Aim 2. Determine the underlying mechanisms by which protein X attenuates inflammation-mediated insulin resistance.
Aim 3. Determine the metabolic function of protein X in vitro and in vivo.
Students are required to learn essential lab techniques and assist with various aspects of the project.
We seek students who those are serious about science, mature and responsible.