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| Status |
Public on Jan 01, 2014 |
| Title |
Identification of Hipk2 as an essential regulator of white fat development |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Homeodomain interacting protein kinase 2 (Hipk2) has previously been implicated in control of several transcription factors involved in embryonic development, apoptosis, cell proliferation and tumour development1–3. Analysis of gene expression in tissues from genetically heterogeneous mouse or human populations can reveal motifs associated with the structural or functional components of the tissue, and may predict roles for genes of unknown function4,5. Here we have applied this network strategy to uncover a novel role for the Hipk2 gene in the transcriptional system controlling adipogenesis. Both in vitro and in vivo models were used to show that knockdown or loss of Hipk2 specifically inhibits white adipose cell differentiation and tissue development. In addition, loss of Hipk2 leads to induction of pockets of multilocular brown fat-like cells in remaining white adipose depots. These cells express markers of brown and beige fat such as uncoupling protein 1 (Ucp1) and transmembrane protein 26 (Tmem26), and thermogenic genes including PPAR-γ coactivator 1a (Ppargc1a), and cell death-inducing DFFA-like effector a (Cidea). These changes are accompanied by increased insulin sensitivity in Hipk2 knock-out mice and reduced high fat diet-induced weight gain, highlighting a potential role for this kinase in diseases such as diabetes and obesity. Our study underscores the versatility and power of a readily available tissue, such as skin, for network modelling of systemic transcriptional programs involved in multiple pathways, including lipid metabolism and adipogenesis.
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| Overall design |
Mammary fat pads from 115 distinct untreated 8 week old [FVB/N x Spret/Ei] x FVB/N Backcross mice
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| Contributor(s) |
Sjölund J, Pelorosso FG, Quigley DA, DelRosario R, Balmain A |
| Citation(s) |
24785298, 34508103 |
| Submission date |
Apr 15, 2013 |
| Last update date |
Sep 29, 2021 |
| Contact name |
David Quigley |
| Organization name |
UCSF
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| Department |
Helen Diller Comprehensive Cancer Center
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| Lab |
Ashworth Lab
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| Street address |
1450 Third St. Room 207
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| City |
San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94158 |
| Country |
USA |
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| Platforms (1) |
| GPL11533 |
[MoGene-1_1-st] Affymetrix Mouse Gene 1.1 ST Array [transcript (gene) version] |
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| Samples (115)
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| Relations |
| BioProject |
PRJNA197207 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE46077_RAW.tar |
481.8 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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