Brown fat can reduce obesity through the dissipation of calories as heat. Recently, a link has been identified between exercise and thermogenesis. We identified interferon regulatory factor 4 (IRF4) as a dominant transcriptional regulator of the thermogenic gene expression program in response to cold. In this application, we hypothesize that IRF4 plays a similar role in exercise-induced thermogenesis. The objective of this application is to determine the mechanisms by which IRF4 exerts its actions at the molecular, cellular and organismal levels. We will accomplish this goal of this proposal by using the tissue-specific IRF4 knockout and overexpression mice as well as in vitro studies. This study will further identify and characterize whether IRF4 participates in the exercise-mediated thermogenesis and the role of IRF4 in muscle in regulating energy homeostasis. Eventually, we believe that the detailed study of IRF4 in the context of metabolism will yield critical insights tat can be exploited therapeutically in the fight against obesity and T2D.

Public Health Relevance

Recently, it has been shown that exercise promotes adipose tissue-mediated thermogenesis via the secretion of myokines. It will be interesting to explore how the signals from adipose tissue to regulate muscle and whether they could function as a treatment for subjects with nonfunctional BAT. The current proposal will allow us to identify and characterize whether IRF4 participates in exercise-mediated thermogenesis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Career Transition Award (K99)
Project #
1K99DK106550-01
Application #
8950846
Study Section
Kidney, Urologic and Hematologic Diseases D Subcommittee (DDK)
Program Officer
Haft, Carol R
Project Start
2015-08-01
Project End
2017-07-31
Budget Start
2015-08-01
Budget End
2016-07-31
Support Year
1
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
Shen, Wen-Jie; Yao, Ting; Kong, Xingxing et al. (2017) Melanocortin neurons: Multiple routes to regulation of metabolism. Biochim Biophys Acta 1863:2477-2485
Yao, Ting; Deng, Zhuo; Gao, Yong et al. (2017) Ire1? in Pomc Neurons Is Required for Thermogenesis and Glycemia. Diabetes 66:663-673
Gao, Yong; Yao, Ting; Deng, Zhuo et al. (2017) TrpC5 Mediates Acute Leptin and Serotonin Effects via Pomc Neurons. Cell Rep 18:583-592
Sun, Jia; Gao, Yong; Yao, Ting et al. (2016) Adiponectin potentiates the acute effects of leptin in arcuate Pomc neurons. Mol Metab 5:882-91