Abstract：
:Uncoupling protein 1 (UCP1) mediates nonshivering thermogenesis and, upon cold exposure, is induced in brown adipose tissue (BAT) and subcutaneous white adipose tissue (iWAT). Here, by high-throughput screening using the UCP1 promoter, we identify Zfp516 as a transcriptional activator of UCP1 as well as PGC1α, thereby promoting a BAT program. Zfp516 itself is induced by cold and sympathetic stimulation through the cAMP-CREB/ATF2 pathway. Zfp516 directly binds to the proximal region of the UCP1 promoter, not to the enhancer region where other transcription factors bind, and interacts with PRDM16 to activate the UCP1 promoter. Although ablation of Zfp516 causes embryonic lethality, knockout embryos still show drastically reduced BAT mass. Overexpression of Zfp516 in adipose tissue promotes browning of iWAT even at room temperature, increasing body temperature and energy expenditure and preventing diet-induced obesity. Zfp516 may represent a future target for obesity therapeutics.
journal_name
Mol Celljournal_title
Molecular cellauthors
Dempersmier J,Sambeat A,Gulyaeva O,Paul SM,Hudak CS,Raposo HF,Kwan HY,Kang C,Wong RH,Sul HSdoi
10.1016/j.molcel.2014.12.005subject
Has Abstractpub_date
2015-01-22 00:00:00pages
235-46issue
2eissn
1097-2765issn
1097-4164pii
S1097-2765(14)00954-Xjournal_volume
57pub_type
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