Diabetes Research and Training Center

Project: Research project

Project Details

Description

Adipose tissue is a metabolic and endocrine organ crucial for whole body insulin sensitivity and energy homeostasis. Adipocytes have the remarkable ability to adapt and respond to environmental cues by regulating adipocyte differentiation and adipokine secretion, thus making adipose tissue one of the key organs that undergoes dynamic changes in obesity and associated type 2 diabetes mellitus. Strong evidence has implicated transcriptional activators as key drivers of adipogenesis as well as insulin sensitivity including peroxisome proliferator activated receptor gamma (PPARg) and CCAAT/enhancer binding proteins (CEBPa, b, g). Thus, further identification of adipose transcriptional networks may begin to explain the physiological connections between adipogenesis and glucose metabolism. Recently, we have found that the transcription factor B Cell lymphoma 6 (BCL6) is highly enriched in differentiated adipocytes. In addition, we performed genome-wide binding site analysis for BCL6 in differentiated adipocytes, which revealed that the BCL6 regulatory circuit overlaps transcriptional networks controlled by CEBP and PPARg. Moreover, in mice harboring adipocyte-specific deletion of BCL6, we observed altered fat distribution with strikingly increased subcutaneous fat mass. Thus, we hypothesize that BCL6 antagonizes insulin sensitivity by attenuating adipogenesis, thereby exacerbating diabetes mellitus. The overarching aims of this proposal seek to establish the role for BCL6 in controlling adipogenic potential and adipocyte transcription, and their associated impacts on whole body glucose metabolism.
StatusFinished
Effective start/end date2/1/151/31/17

Funding

  • University of Chicago (FP035726-02-E//5P30DK020595-38)
  • National Institute of Diabetes and Digestive and Kidney Diseases (FP035726-02-E//5P30DK020595-38)

Fingerprint

Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.