This SuperSeries is composed of the SubSeries listed below.
Toxicogenomics of iron oxide nanoparticles in the nematode C. elegans.
Specimen part
View SamplesSuperparamagnetic Iron Oxide Nanoparticles (SPIONs) are currently being investigated for a range of biomedical applications. Their use have been related with different cytotoxic mechanisms including the generation of oxidative stress and the induction of metal detoxification pathways, among others. We have investigated the molecular mechanisms responsive to in-house fabricated citrate coated SPIONs (C-SPIONs) in the nematode C. elegans to compare in vivo findings with previous in vitro studies. C-SPIONs (500 g/ml) affected the transcriptional response of signal transduction cascades (i.e. TFG-beta), protein processing in the endoplasmic reticulum, and RNA transport, among other biological processes. They also triggered a lysosomal response, indicating a relevant biological role of this cellular compartment in the response to this nanoparticle treatment in C. elegans. Interestingly, other pathways frequently linked to nanotoxicity like oxidative stress or apoptosis were not identified as significantly affected in this genome-wide in vivo study despite the high dose of exposure.
Toxicogenomics of iron oxide nanoparticles in the nematode C. elegans.
Specimen part
View SamplesSuperparamagnetic Iron Oxide Nanoparticles (SPIONs) are currently being investigated for a range of biomedical applications. Their use have been related with different cytotoxic mechanisms including the generation of oxidative stress and the induction of metal detoxification pathways, among others. Different NP coatings are being explored, among them albumin which has been applied in some drugs delivery systems. We have investigated the molecular mechanisms responsive to in-house fabricated SPIONs coated with bovine serum albumin (BSA-SPIONs) in the nematode C. elegans to compare in vivo findings with previous in vitro studies. BSA-SPIONs (500 g/ml) affected the transcriptional response of glycan metabolic pathways related to innate immune response, xenobiotics degradation, and triggered a lysosomal response, indicating a relevant biological role of this cellular compartment in the response to this nanoparticle treatment in C. elegans. Remarkably, key biological functions such as apoptosis or protein processing were not affected with significance despite the high dose of exposure.
Toxicogenomics of iron oxide nanoparticles in the nematode C. elegans.
Specimen part
View SamplesObesity 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)
Nck2 Deficiency in Mice Results in Increased Adiposity Associated With Adipocyte Hypertrophy and Enhanced Adipogenesis.
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View SamplesThe 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
Trans-10, cis-12 conjugated linoleic acid causes inflammation and delipidation of white adipose tissue in mice: a microarray and histological analysis.
Age
View SamplesTrans-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).
Trans-10, cis-12 conjugated linoleic acid activates the integrated stress response pathway in adipocytes.
Cell line
View SamplesTrans-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).
Trans-10, cis-12 conjugated linoleic acid activates the integrated stress response pathway in adipocytes.
Sex, Specimen part
View SamplesTrans-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).
Trans-10, cis-12 conjugated linoleic acid activates the integrated stress response pathway in adipocytes.
Cell line
View SamplesTrans-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).
Trans-10, cis-12 conjugated linoleic acid activates the integrated stress response pathway in adipocytes.
Cell line
View SamplesTunycamcin 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.
Trans-10, cis-12 conjugated linoleic acid activates the integrated stress response pathway in adipocytes.
Cell line
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