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.
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.
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