Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA126821 | ENA |
REPOSITORIES: ENA
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Project description:The nuclear receptor TAK1/TR4/NR2C2 is expressed in several tissues that are important in the control of energy homeostasis. TAK1-deficient (TAK1-/-) mice are resistant to the development of age- and high fat diet (HFD)-induced metabolic syndrome. Biochemical analysis showed significantly lower hepatic triglyceride levels and reduced lipid accumulation in adipose tissue in TAK1-/- mice compared to wild type (WT) mice. Gene expression profiling analysis revealed that the expression of several genes encoding proteins involved in lipid uptake and triglyceride synthesis and storage, including Cidea, Cidec, Mogat1, and CD36, was greatly decreased in the liver of TAK1-/- mice. Moreover, TAK1-/- mice exhibit reduced infiltration of inflammatory cells and expression of inflammatory genes in adipose tissue and were resistant to the development of glucose intolerance and insulin resistance. TAK1-/- mice consume more oxygen and produce more carbon dioxide than WT mice suggesting a higher rate of energy expenditure. Together, these results indicate that TAK1 plays a critical role in the regulation of energy and lipid homeostasis and potentiates the development of metabolic syndrome. Our study suggests that TAK1 might provide a novel therapeutic target in the management of metabolic syndrome. For microarray liver total RNAs were purified from WT and TAK1 KO mice and applied on Agilent mouse genome chip. Liver from 1 year old- WT and TAK1 KO mice.
2010-09-30 | E-GEOD-21903 | biostudies-arrayexpress
Project description:The nuclear receptor TAK1/TR4/NR2C2 is expressed in several tissues that are important in the control of energy homeostasis. TAK1-deficient (TAK1-/-) mice are resistant to the development of age- and high fat diet (HFD)-induced metabolic syndrome. Biochemical analysis showed significantly lower hepatic triglyceride levels and reduced lipid accumulation in adipose tissue in TAK1-/- mice compared to wild type (WT) mice. Gene expression profiling analysis revealed that the expression of several genes encoding proteins involved in lipid uptake and triglyceride synthesis and storage, including Cidea, Cidec, Mogat1, and CD36, was greatly decreased in the liver of TAK1-/- mice. Moreover, TAK1-/- mice exhibit reduced infiltration of inflammatory cells and expression of inflammatory genes in adipose tissue and were resistant to the development of glucose intolerance and insulin resistance. TAK1-/- mice consume more oxygen and produce more carbon dioxide than WT mice suggesting a higher rate of energy expenditure. Together, these results indicate that TAK1 plays a critical role in the regulation of energy and lipid homeostasis and potentiates the development of metabolic syndrome. Our study suggests that TAK1 might provide a novel therapeutic target in the management of metabolic syndrome.
2010-10-01 | GSE21903 | GEO
Project description:Obesity is tightly linked to hepatic steatosis and insulin resistance. One feature of this association is the paradox of selective insulin resistance: insulin fails to suppress hepatic gluconeogenesis but activates lipid synthesis in the liver. How lipid accumulation interferes selectively with some branches of hepatic insulin signaling is not well understood. Here we provide a resource, based on unbiased approaches and established in a simple cell culture system, to enable investigations of the phenomenon of selective insulin resistance. We analyzed the phosphoproteome of insulin-treated human hepatoma cells and identified sites in which palmitate selectively impairs insulin signaling. As an example, we show that palmitate interferes with insulin signaling to FoxO1, a key transcription factor regulating gluconeogenesis, and identify a possible mechanism. This model system, together with our comprehensive characterization of the proteome, phosphoproteome, and lipidome changes in response to palmitate treatment, provides a novel and useful resource for unraveling the mechanisms underlying selective insulin resistance.
2018-02-14 | PXD006395 | Pride
Project description:SHP (small heterodimer partner; NR0B2) belongs to the nuclear hormone receptor superfamily, which regulates numerous developmental and metabolic cellular functions. To study physiological function of SHP, we generated congenic SHP-/- mice on C57Bl/6 background. When the congenic SHP-/- mice were challenged with a western diet (harlan, TD.88137) for 22 weeks, they were resistant to diet induced obesity and hepatic steatosis compared to WT controls. However, their hepatic insulin sensitivity was compromised when assessed with phospho-Akt levels after insulin injection. Therefore, we investigated hepatic gene expression using illumina beadchip array to explore mechanisms underneath the unique liver physiology in SHP-/- mice. Livers were collected from C57Bl/6 wild type and C57Bl/6 SHP-/- mice fed chow or western diet. The 1 microgram of total RNA obtained from individual mouse (n=4 per group) and subjected to illumina beadchip gene expression profiling.
2012-05-16 | E-GEOD-38013 | biostudies-arrayexpress
Project description:The retinoic acid receptor-related orphan receptor a (RORa) is a member of the NR1 subfamily of orphan nuclear hormone receptors. RORa is an important regulator of various biological processes, including cerebellum development, cancer and circadian rhythm. To determine molecular mechanism by which hepatic deletion of RORa induces obesity and insulin resistance, we performed global transcriptome analysis from high-fat diet (HFD)-fed RORa f/f and RORa LKO mouse liver tissues. This analysis provides insight into molecular mechanisms for RORa in high-fat-diet condition.
2017-06-28 | GSE83338 | GEO
Project description:DNA microarray analysis was employed to analyze hepatic gene expression in mice that were protected against HF-induced obesity and liver steatosis (ie HF diets supplemented with lingonberries, blackcurrants or bilberries) and compare to mice who were not protected (HF control) or even experienced increased obesity and fatty liver (HF diet with açai). The study was done to increase understanding of underlying mechanisms of the observed effects.
2015-06-01 | GSE66711 | GEO
Project description:SHP (small heterodimer partner; NR0B2) belongs to the nuclear hormone receptor superfamily, which regulates numerous developmental and metabolic cellular functions. To study physiological function of SHP, we generated congenic SHP-/- mice on C57Bl/6 background. When the congenic SHP-/- mice were challenged with a western diet (harlan, TD.88137) for 22 weeks, they were resistant to diet induced obesity and hepatic steatosis compared to WT controls. However, their hepatic insulin sensitivity was compromised when assessed with phospho-Akt levels after insulin injection. Therefore, we investigated hepatic gene expression using illumina beadchip array to explore mechanisms underneath the unique liver physiology in SHP-/- mice.
2012-05-17 | GSE38013 | GEO
Project description:Analysis of the gene signature of steatosis associated to obesity in hepatocytes of Zucker fa/fa obese rats and their controls; identifying target genes linked to steatosis progression. or Obesity and insulin resistance-associated steatosis can be a non-inflammatory condition affecting hepatocytes or progress to steatohepatitis: a condition that can result in end-stage liver disease. Although molecular events leading to accumulation of lipid droplets in the liver have been identified individually, the complexity of the condition suggested that emergent target would be uncovered by a more comprehensive examination. Then, this study was aimed at establishing a gene signature of steatosis in hepatocytes and at identifying target genes linked to steatosis progression. Using Affymetrix oligonucleotide arrays, we compared transcriptomes of hepatocytes isolated from Zucker "fa/fa" obese rats with three different age-related grades of steatosis with those of their counterpart non-steatotic cells.
2008-07-31 | E-MEXP-1414 | biostudies-arrayexpress
Project description:Hepatic lipogenesis is a central aspect of the feeding response and is aberrantly induced in the progression of fatty liver disease. Liver X receptors (LXRs) and sterol regulatory element-binding protein 1c (SREBP1c) are potent activators of the lipogenic gene program that promote triglyceride synthesis and hepatic steatosis in the insulin-resistant state. To date, key protein components of the LXR-SREBP1c axis have been uncovered that mediate transcriptional activation of SREBP1c by LXRs and nutrient and hormonal regulation. However, whether this regulatory pathway interfaces with long noncoding RNAs (lncRNAs) remains largely unexplored. Here we show that hepatic expression of Blnc1, a regulator of brown adipocyte development, is strongly associated with adiposity and liver fat content in mice. Blnc1 is required for the induction of SREBP1c and hepatic lipogenic genes in response to LXR activation. CRISPR/Cas9-mediated liver-specific inactivation of Blnc1 abrogates high fat diet-induced hepatic steatosis and insulin resistance. We further observed that liver Blnc1 expression is elevated in a mouse model of nonalcoholic steatohepatitis (NASH). Mice lacking Blnc1 in the liver are protected from diet-induced NASH and exhibit attenuated liver injury, inflammation and liver fibrosis. At the molecular level, proteomic analysis of the Blnc1 ribonucleoprotein complex in the liver identified endothelial differentiation related factor 1 (EDF1) as a component of the LXR transcriptional complex that acts in concert with Blnc1 to stimulate SREBP1c expression. These findings uncover a lncRNA ribonucleoprotein complex that licenses obesity-linked activation of hepatic lipogenesis and NAFLD pathogenesis.
2018-12-21 | GSE108609 | GEO
Project description:Nuclear receptor, RORa plays a critical role in obesity-associated inflammation, hepatic steatosis, and insulin resistance
| PRJNA130775 | ENA