IRF4 is a key thermogenic transcriptional partner of PGC-1α.

Cell
Authors
Keywords
Abstract

Brown fat can reduce obesity through the dissipation of calories as heat. Control of thermogenic gene expression occurs via the induction of various coactivators, most notably PGC-1α. In contrast, the transcription factor partner(s) of these cofactors are poorly described. Here, we identify interferon regulatory factor 4 (IRF4) as a dominant transcriptional effector of thermogenesis. IRF4 is induced by cold and cAMP in adipocytes and is sufficient to promote increased thermogenic gene expression, energy expenditure, and cold tolerance. Conversely, knockout of IRF4 in UCP1(+) cells causes reduced thermogenic gene expression and energy expenditure, obesity, and cold intolerance. IRF4 also induces the expression of PGC-1α and PRDM16 and interacts with PGC-1α, driving Ucp1 expression. Finally, cold, β-agonists, or forced expression of PGC-1α are unable to cause thermogenic gene expression in the absence of IRF4. These studies establish IRF4 as a transcriptional driver of a program of thermogenic gene expression and energy expenditure.

Year of Publication
2014
Journal
Cell
Volume
158
Issue
1
Pages
69-83
Date Published
2014 Jul 03
ISSN
1097-4172
URL
DOI
10.1016/j.cell.2014.04.049
PubMed ID
24995979
PubMed Central ID
PMC4116691
Links
Grant list
R01 DK085171 / DK / NIDDK NIH HHS / United States
P30 DK043351 / DK / NIDDK NIH HHS / United States
R01 DK054477 / DK / NIDDK NIH HHS / United States
K08 DK097303 / DK / NIDDK NIH HHS / United States
R01 DK077097 / DK / NIDDK NIH HHS / United States
R01 DK31405 / DK / NIDDK NIH HHS / United States
R01 DK031405 / DK / NIDDK NIH HHS / United States
T32 DK007516 / DK / NIDDK NIH HHS / United States