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
Research Transition Award (R00)
Project #
4R00DK106550-03
Application #
9532340
Study Section
Special Emphasis Panel (NSS)
Program Officer
Haft, Carol R
Project Start
2017-08-15
Project End
2020-08-14
Budget Start
2017-08-15
Budget End
2018-08-14
Support Year
3
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Kong, Xingxing; Yao, Ting; Zhou, Peng et al. (2018) Brown Adipose Tissue Controls Skeletal Muscle Function via the Secretion of Myostatin. Cell Metab 28:631-643.e3