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SRP050090
Mus musculus
4 Downloadable Samples
Illumina HiSeq 2000
Description
Obesity is linked to the development of metabolic disorders. Expansion of white adipose tissue (WAT) from hypertrophy of pre-existing adipocytes and/or differentiation of precursors into new mature adipocytes contributes to obesity. We found that Nck2 expression is largely restricted to WAT, raising the hypothesis that it may play a unique function in that tissue. Using mice lacking Nck2, we found that Nck2 regulates adipocyte hypertrophy thus contributing to increased adiposity and progressive glucose intolerance, insulin resistance and hepatic steatosis. These findings were recapitulated in humans such that Nck2 expression in omental WAT was inversely correlated with the degree of obesity. Mechanistically, Nck2 deficiency promoted the induction of an adipocyte differentiation program and signaling by the PERK-eIF2a-ATF4 pathway in agreement with a role for the unfolded protein response in adipogenesis. These findings uncover Nck2 as a novel regulator of adipogenesis and that perturbation in its functionality contributes to adiposity-related metabolic disorders. Overall design: Differential gene expression profile between epididymal white adipose tissue of Nck2-/- and Nck2+/+ mice by RNA sequencing (Illumina HiSEq 2000)
Publication Title
Nck2 Deficiency in Mice Results in Increased Adiposity Associated With Adipocyte Hypertrophy and Enhanced Adipogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 28 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The white adipose tissue (WAT) rapidly loses mass when mice are fed a diet containing trans-10, cis-12 conjugated linoleic acid (t10c12 CLA). A microarray analysis of WAT due to CLA feeding was performed to better define the processes and genes involved. WAT weight decreased by ca. 80% over 17 days of feeding a 0.5% t10c12 CLA diet. The lipid volume decreased by 90% and the number of adipocytes and total cells were reduced by15% and 47%, respectively. Microarray profiling of replicated pools of control and treated mice (n=140) at seven time points over the 17day feeding indicated between 2798 to 4318 genes showed mRNA changes of 2-fold or more. Transcript levels for genes of glucose and fatty acid import or biosynthesis were significantly reduced. A prolific inflammation response was indicated by the 2 to100-fold induction of many cytokine transcripts, including those for IL-6, IL1?, TNF ligands, and CXC family members
Publication Title
Trans-10, cis-12 conjugated linoleic acid causes inflammation and delipidation of white adipose tissue in mice: a microarray and histological analysis.
Sample Metadata Fields
Age
View Samples- Mus musculus
- 24 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Trans-10, Cis-12 conjugated linoleic acid (t10c12 CLA) causes fat loss in mouse 3T3-L1 adipocyte tissue culture. The early transcriptome changes were analyzed using high-density microarrays to better characterize the signaling pathways responding to t10c12 CLA. Their gene expression responses between 4 to 24 hr after treatment showed a common set of early gene expression changes indicative of an integrated stress response (ISR).
Publication Title
Trans-10, cis-12 conjugated linoleic acid activates the integrated stress response pathway in adipocytes.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Trans-10, Cis-12 conjugated linoleic acid (t10c12 CLA) causes fat loss in mouse white adipose tissue (WAT). The early transcriptome changes in WAT were analyzed using high-density microarrays to better characterize the signaling pathways responding to t10c12 CLA. Their gene expression responses between 4 to 24 hr after treatment showed a common set of early gene expression changes indicative of an integrated stress response (ISR).
Publication Title
Trans-10, cis-12 conjugated linoleic acid activates the integrated stress response pathway in adipocytes.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Trans-10, Cis-12 conjugated linoleic acid (t10c12 CLA) causes fat loss in mouse white adipose tissue (WAT) and 3T3-L1 adipocyte tissue culture; however in preadipocyte tissue (this series) the UPS/ISR and fat loss is not detected. The early transcriptome changes in 3T3-L1 preadipocyte tissue culture were analyzed using high-density microarrays to better characterize the signaling pathways responding to t10c12 CLA. Their gene expression responses between 4 to 12 hr after treatment do not show a set of genes indicative of an integrated stress response (ISR).
Publication Title
Trans-10, cis-12 conjugated linoleic acid activates the integrated stress response pathway in adipocytes.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Trans-10, Cis-12 conjugated linoleic acid (t10c12 CLA) causes fat loss in mouse 3T3-L1 adipocyte tissue culture; however cis-9, trans-11 CLA does not (this series). The early transcriptome changes were analyzed using high-density microarrays to better characterize the signaling pathways responding to c9t11 CLA. Their gene expression responses between 8 to 12 hr after treatment showed no gene expression changes indicative of an integrated stress response (ISR).
Publication Title
Trans-10, cis-12 conjugated linoleic acid activates the integrated stress response pathway in adipocytes.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Tunycamcin induces UPR/ISR and Inflammation in mouse 3T3-L1 adipocyte tissue culture. The early transcriptome changes were analyzed using high-density microarrays to better characterize the signaling pathways responding to tunicamycin, to be compared with similar experiments with CLA as the treatment. Their gene expression responses between 4 to 12 hr after treatment showed a common set of early gene expression changes indicative of a UPR/Inflammation stress response.
Publication Title
Trans-10, cis-12 conjugated linoleic acid activates the integrated stress response pathway in adipocytes.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Akt1, a serine-threonine protein kinase member of the PKB/Akt gene family, plays a critical role in the regulation of several cellular processes including cell proliferation and apoptosis. In this study, we utilized Akt1+/+ and Akt1-/- C57/Bl6 female mice to demonstrate that Akt1 is required for normal mammary gland postnatal development and homeostasis. Akt1 deficiency resulted in severely delayed postnatal mammary gland growth as well as a significant decrease in the number of terminal end buds during puberty. Adult Akt1-/- mammary glands exhibited significantly fewer alveolar buds coupled with a significant increase in epithelial cell apoptosis compared to their wild-type counterparts. Microarray analysis revealed that Akt1 deficiency resulted in several altered gene expression changes and biological processes in adult mammary glands, including organismal development, cell death, and tissue morphology. Of particular importance, a significant decrease in expression of Btn1a1, a gene involved in milk lipid secretion, was observed in Akt1-/- mammary glands by both microarray and RT-PCR validation.
Publication Title
Akt1 is essential for postnatal mammary gland development, function, and the expression of Btn1a1.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 55 Downloadable Samples
- Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482), Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Epigenome-wide and transcriptome-wide analyses reveal gestational diabetes is associated with alterations in the human leukocyte antigen complex.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 55 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20), Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)
Description
Gestational diabetes mellitus (GDM) affects approximately 18% of pregnancies in the United States and increases the risk of adverse health outcomes in the offspring. These adult disease propensities may be set by anatomical and molecular alterations in the placenta associated with GDM. To assess the mechanistic aspects of fetal programming, we measured genome-wide methylation (Infinium HumanMethylation450 Beadchips) and expression (Affymetrix Transcriptome Microarrays) in placental tissue of 41 GDM cases and 41 matched pregnancies without maternal complications from the Harvard Epigenetic Birth Cohort. Specific transcriptional and epigenetic perturbations associated with GDM status included alterations in the major histocompatibility complex (MHC) region, which were validated in an independent cohort, the Rhode Island Child Health Study. Gene ontology enrichment among gene regulation influenced by GDM revealed an over-representation of immune response pathways among differential expression, reflecting these coordinated changes in the MHC region. Our study represents the largest investigation of transcriptomic and methylomic differences associated with GDM, providing comprehensive insight into the molecular basis of GDM induced fetal (re)programming.
Publication Title
Epigenome-wide and transcriptome-wide analyses reveal gestational diabetes is associated with alterations in the human leukocyte antigen complex.
Sample Metadata Fields
Specimen part
View Samples