This proposal is designed to study the role of early B cell factors (EBFs) in adipocyte biology. We have shown that EBF1 and EBF2 are required for fat cell development, and may play a significant role in governing gene expression and metabolism in fat cells. This proposal has three major Aims. First, we intend to characterize the mechanism of EBF1 action in adipogenesis, focusing on two recently discovered splice variants and on the role of EPAS1 as a mediator of the EBF1 pro-adipogenic effect. Second, we will investigate the role of EBF1 and EBF2 in metabolic physiology in vitro, using pair-wise gain-of-function and loss-of-function techniques. Specifically, we hypothesize that EBF1 and EBF2 repress lipogenesis and promote fatty acid oxidation in cultured fat cells. Finally, we will examine study the role of EBF1 and EBF2 in several in vivo models of adipocyte biology, including conditional gene ablation in adipocytes. These studies will help us to gain insight into novel transcriptional pathways in adipocyte biology, which should enable us to develop rational therapies for metabolic disease.

Public Health Relevance

EBFs play an important role in governing transcriptional pathways in adipocytes. Understanding these pathways better will allow us to design rational strategies to combat diseases that involve adipocytes, such as obesity and lipodystrophy. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK078061-01A2
Application #
7522685
Study Section
Cellular Aspects of Diabetes and Obesity Study Section (CADO)
Program Officer
Haft, Carol R
Project Start
2008-07-01
Project End
2012-04-30
Budget Start
2008-07-01
Budget End
2009-04-30
Support Year
1
Fiscal Year
2008
Total Cost
$361,250
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02215
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Griffin, Michael J; Zhou, Yiming; Kang, Sona et al. (2013) Early B-cell factor-1 (EBF1) is a key regulator of metabolic and inflammatory signaling pathways in mature adipocytes. J Biol Chem 288:35925-39
Kang, Sona; Akerblad, Peter; Kiviranta, Riku et al. (2012) Regulation of early adipose commitment by Zfp521. PLoS Biol 10:e1001433
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