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GSE35011
Mus musculus
8 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Brown adipose tissue dissipates energy through heat and functions as a defense against cold and obesity. PPAR ligands have been shown to induce the browning of white adipocytes; however, the underlying mechanisms remain unclear. Here we show that PPAR ligands require full agonism to induce a brown fat gene program preferentially in subcutaneous white adipose. These effects require expression of PRDM16, a factor that controls the development of classical brown fat. Depletion of PRDM16 blunts the effects of the PPAR agonist rosiglitazone on the induced brown fat gene program. Conversely, PRDM16 and rosiglitazone synergistically activate the brown fat gene program in vivo. This synergy is tightly associated with an increased accumulation of PRDM16 protein, due in large measure to an increase in the half-life of the protein in agonist treated cells. Identifying compounds that stabilize PRDM16 protein may represent a novel therapeutic pathway for the treatment of obesity and diabetes.
Publication Title
PPARγ agonists induce a white-to-brown fat conversion through stabilization of PRDM16 protein.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Medium conditioned by LLC cells stimulates thermogenic gene expression when added onto primary adipocytes. We generated single cell colonies from parental LLC cells. Media conditioned by the subclones stimulated thermogenic gene expression in primary adipocytes at varying degrees.
Publication Title
Tumour-derived PTH-related protein triggers adipose tissue browning and cancer cachexia.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
PPAR is a member of the nuclear receptor family for which agonist ligands have anti-growth effects. However, clinical studies using PPAR ligands as a monotherapy failed to show a beneficial effect. Here we have studied the effects of PPAR activation with chemotherapeutic agents in current use for specific cancers. We observed a striking synergy between rosiglitazone and platinum-based drugs in several different cancers both in vitro and using transplantable and chemically induced spontaneous tumor models. The effect appears to be due in part to PPAR-mediated downregulation of metallothioneins, proteins that have been shown to be involved in resistance to platinum-based therapy. These data strongly suggest combining PPAR agonists and platinum-based drugs for the treatment of certain human cancers
Publication Title
Synergy between PPARgamma ligands and platinum-based drugs in cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
PRDM16 is a 140 kDa transcriptional coregulatory protein. PRDM16 has been shown to function as a bi-directional switch in brown fat cell fate by stimulating the development of brown fat cells from myf-5 positive myoblastic precursors.
Publication Title
Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-beta transcriptional complex.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Skeletal muscle must perform a wide range of kinds of work, and different fiber types have evolved to accommodate these different tasks. The attributes of fibers are determined in large part by the coordinated regulation of oxidative capacity, as reflected by mitochondrial content, and the specific makeup of myofibrillar proteins. Adult muscle fibers contain four myosin heavy chain isotypes: I, IIa, IIx and IIb. Type I and IIa fibers have slower twitches and are rich in mitochondria, while type IIb fibers are fast-twitch and predominantly glycolytic. The intermediate IIx fibers are less well understood. Previous work had shown that the transcriptional coactivator PGC-1 alpha could drive the formation of type I and IIa muscle fibers. We show here that mice with transgenic expression of PGC-1 beta in skeletal muscle results in marked induction of IIx fibers. The fibers in transgenic mice are rich in mitochondria and are highly oxidative. As a result, PGC-1 beta transgenic animals can perform oxidative activity for longer and at higher work loads than wild type animals. In cell culture, PGC-1 beta coactivates the MEF2 family of transcription factors to stimulate the MHC IIx promoter. Together, these data indicate that PGC-1 beta is sufficient to drive the formation in vivo of highly oxidative fibers with type IIx characteristics.
Publication Title
The transcriptional coactivator PGC-1beta drives the formation of oxidative type IIX fibers in skeletal muscle.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Parathyroid hormone (PTH) and PTH-related protein (PTHrP) are involved in cachexia associated with chronic kidney disease and cancer respectively. Tumor-derived PTHrP triggers adipose tissue browning and thereby leads to wasting of fat tissue in tumor-bearing mice. Similarly, elevated in 5/6 nephrectomized mice, PTH stimulates adipose tissue browning and wasting. Mice lacking the PTH/PTHrP receptor in their fat tissue are resistant to wasting of both adipose tissue and skeletal muscle. Therefore, the PTH/PTHrP signaling in adipocytes should activate various pathways that contribute to hypermetabolism and muscle wasting.
Publication Title
PTH/PTHrP Receptor Mediates Cachexia in Models of Kidney Failure and Cancer.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
ES cell-derived neurons of forebrain identity were isolated by magnetic sorting, cultured for 7 days and transduced with either Nurr1 or eGFP lentivirus. After an additional 12 h in culture, mRNA was isolated and subjected to microarray analysis.
Publication Title
NR4A orphan nuclear receptors as mediators of CREB-dependent neuroprotection.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Committed preadipocyte fibroblasts were genetically labelled in transgenic mice by expressing GFP under the control of the locus for Zfp423, a gene controlling preadipocyte determination. These mice are herein referred to as Zfp423-GFP mice. The overall goal was to identify genes differentially expressed between adipogenic GFP+ firboblasts and non-adipogenic GFP- fibroblasts from either inguinal or epididymal fat stromal vascular cultures obtained from Zfp423-GFP mice.
Publication Title
Zfp423 expression identifies committed preadipocytes and localizes to adipose endothelial and perivascular cells.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The aim of this study was to identify genes expressed selectively in brown adipose tissue as compared to white adipose tissue from the same animals. This analysis provides a gene set that is brown and white adipose selective.
Publication Title
Transcriptional control of brown fat determination by PRDM16.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
PGC1a is a transcriptional coactivator that regulates energy metabolism. PGC1a is highly expressed in a subset of melanoma tumors and cell lines. We generated gene-expression profile of control and PGC1alpha depleted A375P melanoma cells, a melanoma cell line that expresses very high levels of PGC1a to investigate the role of this gene in melanoma.
Publication Title
PGC1α expression defines a subset of human melanoma tumors with increased mitochondrial capacity and resistance to oxidative stress.
Sample Metadata Fields
Specimen part
View Samples