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Status |
Public on Jan 23, 2020 |
Title |
Fibroblast Growth Factor-21 Regulates PPARγ Activity and the Antidiabetic Actions of Thiazolidinediones |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
Fibroblast growth factor-21 (FGF21) is a circulating hepatokine that beneficially affects carbohydrate and lipid metabolism. Here we report that FGF21 is also an inducible, fed-state autocrine factor in adipose tissue that functions in a feed-forward loop to regulate the activity of peroxisome proliferator-activated receptor γ (PPARγ), a master transcriptional regulator of adipogenesis. FGF21-knockout (KO) mice display defects in PPARγ signaling including decreased body fat and attenuation of PPARγ-dependent gene expression. Moreover, FGF21-KO mice are refratory to both the beneficial, insulin-sensitizing effects and the detrimental weight gain and edema side effects of the PPARγ agonist rosiglitazone. This loss of function in FGF21-KO mice is coincident with a marked increase in the sumoylation of PPARγ, which reduces its transcriptional activity. Adding back FGF21 prevents sumoylation and restores PPARγ activity. Collectively, these results reveal FGF21 as a key mediator of the physiologic and pharmacologic actions of PPARγ.
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Overall design |
RNA was prepared from epididymal white adipose tissue of Diet-induced Obesity (DIO) wild-type and FGF21-KO mice treated with rosiglitazone or vehicle for 14 days (2 pools of 2 mice per condition).
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Contributor(s) |
Yu RT, Dutchak PA, Kliewer SA |
Citation(s) |
22304921 |
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Submission date |
Nov 14, 2011 |
Last update date |
Apr 23, 2020 |
Contact name |
Ruth T Yu |
Organization name |
Salk Institute
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Department |
Gene Expression Lab
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Lab |
Ronald Evans
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Street address |
10010 N Torrey Pines Rd
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City |
La Jolla |
State/province |
CA |
ZIP/Postal code |
92037 |
Country |
USA |
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Platforms (1) |
GPL6885 |
Illumina MouseRef-8 v2.0 expression beadchip |
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Samples (16)
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GSM832748 |
wild-type c57b6/sv129 mixed bkg WAT, DIO, biological replicate 1 |
GSM832749 |
wild-type c57b6/sv129 mixed bkg WAT, DIO, technical replicate of bio rep 1 |
GSM832750 |
wild-type c57b6/sv129 mixed bkg WAT, DIO, biological replicate 2 |
GSM832751 |
wild-type c57b6/sv129 mixed bkg WAT, DIO, technical replicate of bio rep 2 |
GSM832752 |
wild-type c57b6/sv129 mixed bkg WAT, DIO, treated with Rosiglitazone, biological replicate 1 |
GSM832753 |
wild-type c57b6/sv129 mixed bkg WAT, DIO, treated with Rosiglitazone, technical replicate of bio rep 1 |
GSM832754 |
wild-type c57b6/sv129 mixed bkg WAT, DIO, treated with Rosiglitazone, biological replicate 2 |
GSM832755 |
wild-type c57b6/sv129 mixed bkg WAT, DIO, treated with Rosiglitazone, technical replicate of bio rep 2 |
GSM832756 |
FGF21 KO, WAT, DIO, biological replicate 1 |
GSM832757 |
FGF21 KO, WAT, DIO, technical replicate of bio rep 1 |
GSM832758 |
FGF21 KO, WAT, DIO, biological replicate 2 |
GSM832759 |
FGF21 KO, WAT, DIO, technical replicate of bio rep 2 |
GSM832760 |
FGF21 KO, WAT, DIO, treated with Rosiglitazone, biological replicate 1 |
GSM832761 |
FGF21 KO, WAT, DIO, treated with Rosiglitazone, technical replicate of bio rep 1 |
GSM832762 |
FGF21 KO, WAT, DIO, treated with Rosiglitazone, biological replicate 2 |
GSM832763 |
FGF21 KO, WAT, DIO, treated with Rosiglitazone, technical replicate of bio rep 2 |
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Relations |
BioProject |
PRJNA148309 |
Supplementary file |
Size |
Download |
File type/resource |
GSE33684_RAW.tar |
3.1 Mb |
(http)(custom) |
TAR |
GSE33684_non-normalized.txt.gz |
4.7 Mb |
(ftp)(http) |
TXT |
GSE33684_normalized.txt.gz |
4.7 Mb |
(ftp)(http) |
TXT |
GSE33684_statistics.txt.gz |
139.6 Kb |
(ftp)(http) |
TXT |
Processed data included within Sample table |
Processed data are available on Series record |
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