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Cell DOI:10.1016/j.cell.2014.04.049

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

Publication TypeJournal Article
Year of Publication2014
AuthorsKong, X, Banks, A, Liu, T, Kazak, L, Rao, RR, Cohen, P, Wang, X, Yu, S, Lo, JC, Tseng, Y-H, Cypess, AM, Xue, R, Kleiner, S, Kang, S, Spiegelman, BM, Rosen, ED
Date Published2014 Jul 03
KeywordsAdipocytes, Adipose Tissue, Brown, Adrenergic beta-3 Receptor Agonists, Animals, Cold Temperature, Cyclic AMP, Energy Metabolism, Humans, Interferon Regulatory Factors, Ion Channels, Mice, Mitochondria, Mitochondrial Proteins, Obesity, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Thermogenesis, Thinness, Transcription Factors, Transcriptional Activation, Uncoupling Protein 1

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.


Alternate JournalCell
PubMed ID24995979
PubMed Central IDPMC4116691
Grant ListR01 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