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GSE71101
Mus musculus
8 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Multipotent C3H10T1/2 cells can be induced to differentiate into mature brown adipocytes by 3-days BMP7 pretreatment followed by standard adipogenic induction.
Publication Title
MicroRNA-455 regulates brown adipogenesis via a novel HIF1an-AMPK-PGC1α signaling network.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Both environmental and genetic factors play important roles in the development of the metabolic syndrome. To elucidate how these factors interact under normal conditions, C57Bl/6 (B6) and 129S6/SvEvTac (129) mice were placed on a low-fat or high-fat diet. Liver samples were extracted and hybridized to Affymetrix Genome U74 (version 2) arrays.
Publication Title
Effects of diet and genetic background on sterol regulatory element-binding protein-1c, stearoyl-CoA desaturase 1, and the development of the metabolic syndrome.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 48 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Insulin resistance in skeletal muscle is a key phenotype associated with type 2 diabetes (T2D) and is even present in offspring of diabetic parents. However, molecular mediators of insulin resistance remain unclear. We find that the top-ranking gene set in expression analysis of muscle from humans with T2D and normoglycemic insulin resistant subjects with parental family history (FH+) of T2D is increased expression of actin cytoskeleton genes regulated by serum response factor (SRF) and its coactivator MKL1. Furthermore, the SRF activator STARS is upregulated in FH+ and T2D and inversely correlated with insulin sensitivity. These patterns are recapitulated in insulin resistant mice, and linked to alterations in two other regulators of this pathway: reduced G-actin and increased nuclear localization of MKL1. Both genetic and pharmacologic manipulation of STARS/MKL1/SRF pathway significantly alter insulin action: 1) Overexpression of MKL1 or reduction in G-actin decreased insulin-stimulated Akt phosphorylation; 2) reduced STARS expression increased insulin signalling and glucose uptake, and 3) SRF inhibition by CCG-1423 reduced nuclear MKL1, improved glucose uptake, and improved glucose tolerance in insulin resistant mice in vivo. Thus, SRF pathway alterations are a signature of insulin resistance which may also contribute to T2D pathogenesis and be a novel therapeutic target.
Publication Title
Increased SRF transcriptional activity in human and mouse skeletal muscle is a signature of insulin resistance.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Despite a high degree of homology, insulin and IGF-1 receptors (IR/IGF1R) mediate distinct cellular and physiological functions. Here, using chimeric and site-mutated receptors, we demonstrate how domain differences between IR and IGF1R contribute the distinct functions of these receptors.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We and others have previously observed that adipocytes and preadipocytes taken from different adipose tissue depots are characterized by differential expression of developmental and patterning genes (Dankel et al., 2010; Ferrer-Lorente et al., 2014; Gesta et al., 2006; Lee et al., 2017a; Lee et al., 2013; Macotela et al., 2012; Tchkonia et al., 2007; Yamamoto et al., 2010). To investigate how adipocyte heterogeneity and differences in the expression of developmental genes might impact the biology of adipocytes and preadipocytes, we created preadipocyte cell lines from the stromovascular fraction (SVF) isolated from the scapular white, inguinal, perigonadal, perirenal, and mesenteric fat pads of 6-week old male Immortomouse (Jat et al., 1991).During routine culture of the subcutaneous and visceral/perigonadal clonal cell lines, we observed extreme variation in media acidification rates that was unrelated to the fat pad of origin, the differentiation capacity of the cells, or the rate of their proliferation, suggesting metabolic heterogeneity. To further investigate this possibility, 24 clonal cell lines (12 each from subcutaneous and perigonadal fat) were selected based on variable media acidification rates, and their mRNA expression pattern determined by microarray analysis. The expression data was clustered using three different algorythms, and the consensus was used to categorize each type of adipose tissue.
Publication Title
Developmental and functional heterogeneity of white adipocytes within a single fat depot.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Hepatic lipid accumulation is an important complication of obesity linked to risk for type 2 diabetes. To identify novel transcriptional changes in human liver which could contribute to hepatic lipid accumulation and associated insulin resistance and type 2 diabetes (DM2), we evaluated gene expression and gene set enrichment in surgical liver biopsies from 13 obese (9 with DM2) and 5 control subjects, obtained in the fasting state at the time of elective abdominal surgery for obesity or cholecystectomy. RNA was isolated for cRNA preparation and hybridized to Affymetrix U133A microarrays.
Publication Title
Thyroid hormone-related regulation of gene expression in human fatty liver.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Alternative mRNA splicing provides transcript diversity and has been proposed to contribute to several human diseases. Here, we demonstrate that expression of genes regulating RNA processing is decreased in both liver and skeletal muscle of obese humans. To determine the metabolic impact of reduced splicing factor expression, we further evaluated the splicing factor, SFRS10, identified as down-regulated in obese human liver and skeletal muscle and in high fat fed rodents. siRNA-mediated reductions in SFRS10 expression induced lipogenesis and lipid accumulation in cultured hepatocytes. Moreover, SFRS10 heterozygous mice have both increased hepatic lipogenic gene expression and hypertriglyceridemia. We also demonstrate that LPIN1, a key regulator of lipid metabolism, is a splicing target of SFRS10, with reduced SFRS10 levels favoring the lipogenic isoform of LPIN1. Importantly, LPIN1-specific siRNA abolished the lipogenic effects of decreased SFRS10 expression. Together, our results indicate reduced expression of SFRS10 alters LPIN1 splicing and induces lipogenesis, demonstrating that reduced splicing factor expression observed in human tissues may contribute to metabolic phenotypes associated with human obesity.
Publication Title
Expression of the splicing factor gene SFRS10 is reduced in human obesity and contributes to enhanced lipogenesis.
Sample Metadata Fields
Age, Subject
View Samples- Mus musculus
- 17 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
The brain is the most cholesterol-rich organ in the body, most of which comes from in situ synthesis. Here we demonstrate that in insulin-deficient diabetic mice, there is a reduction in expression of the major transcriptional regulator of cholesterol metabolism, SREBP-2, and its downstream genes in the hypothalamus and other areas of the brain, leading to a reduction in brain cholesterol synthesis and synaptosomal cholesterol content. These changes are due, at least in part, to direct effects of insulin to regulate these genes in neurons and glial cells and can be corrected by intracerebroventricular injections of insulin. Knockdown of SREBP-2 in cultured neurons causes a decrease in markers of synapse formation and reduction of SREBP-2 in the hypothalamus of mice using shRNA results in increased feeding and weight gain. Thus, insulin and diabetes can alter brain cholesterol metabolism, and this may play an important role in the neurologic and metabolic dysfunction observed in diabetes and other disease states.
Publication Title
Diabetes and insulin in regulation of brain cholesterol metabolism.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We found that hyperglycemia and elevated fatty acids in diabetes could activate protein kinase C- isoforms and selectively induce insulin resistance via inhibiting vascular insulin signaling.
Publication Title
Insulin decreases atherosclerosis by inducing endothelin receptor B expression.
Sample Metadata Fields
Age, Specimen part, Disease, Disease stage, Treatment
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Exercise training improves whole body glucose homeostasis through effects largely attributed to adaptations in skeletal muscle; however, training also affects other tissues including adipose tissue. To determine if exercise-induced adaptations to adipose tissue contribute to training-induced improvements in glucose homeostasis, subcutaneous white adipose tissue (scWAT) from trained or sedentary donor mice was transplanted into the visceral cavity of sedentary recipients. Remarkably, nine days post-transplantation, mice receiving trained scWAT had improved glucose tolerance and enhanced insulin sensitivity compared to mice transplanted with sedentary scWAT or sham-treated mice. Mice transplanted with trained scWAT had increased insulin-stimulated glucose uptake in tibialis anterior and soleus muscles and brown adipose tissue, suggesting that the transplanted scWAT exerted endocrine effects. Furthermore, the deleterious effects of high-fat feeding on glucose tolerance and insulin sensitivity were completely reversed if high-fat fed recipient mice were transplanted with trained scWAT. In additional experiments, voluntary exercise training by wheel running for only 11 days resulted in profound changes in scWAT including increased expression of 1550 genes involved in numerous cellular functions, including metabolism. Exercise training causes adaptations to scWAT that elicit metabolic improvements in other tissues, demonstrating a previously unrecognized role for adipose tissue in the beneficial effects of exercise on systemic glucose homeostasis.
Publication Title
A novel role for subcutaneous adipose tissue in exercise-induced improvements in glucose homeostasis.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples