GENE EXPRESION PROFILE OF HEPATIC PROGENITOR CELLS FROM Ptpn1+/+ AND Ptpn1-/- MICE AFTER PALMITIC ACID TREATMENT
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE199644 | GEO | 2022/04/01
REPOSITORIES: GEO
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Project description:GENE EXPRESION PROFILE OF HEPATIC PROGENITOR CELLS FROM Ptpn1+/+ AND Ptpn1-/- MICE AFTER PALMITIC ACID TREATMENT
| PRJNA821058 | ENA
Project description:We report here the deep sequencing of the mRNA from peritoneal exudate cells (macrophages) purified from wildtype or Ptpn1 (PTP1B) knockout mice, either treated or untreated with IL-10. In periotenal macrophages IL-10 activates the transcription factor STAT3 to execute and anti-inflammatory gene expression programme. The tyrosine phosphatase PTPN1 targets STAT3 for dephosphorylation and leads to the deactivation of STAT3. In this study we examined the role of PTP1B in controlling the normal homeostatic level phosphorylation of STAT3 by comparing the IL-10/STAT3-mediated anti-inflammatory gene expression programme. We find that loss of PTP1B leads to an up-regulation of the activity of STAT3, both at the level of phosphorylation and also in enhanced expression of anti-inflammatory gene products. RNA-seq of wildtype and Ptpn1 (PTP1B) knockout mouse peritoneal macrophages, treated or untreated with IL-10
2014-05-12 | E-GEOD-49449 | biostudies-arrayexpress
Project description:We report here the deep sequencing of the mRNA from peritoneal exudate cells (macrophages) purified from wildtype or Ptpn1 (PTP1B) knockout mice, either treated or untreated with IL-10. In periotenal macrophages IL-10 activates the transcription factor STAT3 to execute and anti-inflammatory gene expression programme. The tyrosine phosphatase PTPN1 targets STAT3 for dephosphorylation and leads to the deactivation of STAT3. In this study we examined the role of PTP1B in controlling the normal homeostatic level phosphorylation of STAT3 by comparing the IL-10/STAT3-mediated anti-inflammatory gene expression programme. We find that loss of PTP1B leads to an up-regulation of the activity of STAT3, both at the level of phosphorylation and also in enhanced expression of anti-inflammatory gene products.
2014-05-12 | GSE49449 | GEO
Project description:Background: Palmitic acid (PAM) can be provided in the diet or synthesized via de novo lipogenesis (DNL) primarily from glucose. Preclinical work on the origin of brain PAM during development is scarce and contrasts results on the origin of adult brain PAM. Here, we utilize naturally occurring carbon isotope ratios (13C/12C; δ13C) and RNA sequencing to uncover the origin of brain PAM, and pathways involved in maintaining brain PAM, respectively, during development. maintaining brain PAM, respectively, during development. Methods: Dams were equilibrated onto diets low (<2%), medium (47%) or high (>95%) in PAM prior to breeding. Dietary PAM was depleted in δ13C, while dietary sugars were enriched. Offspring stayed on the respective dam diet and were euthanized at postnatal day 0, 10, 21, and day 35. Pup liver and brain fatty acids were quantified, after which, tissue δ13C-PAM was measured by compound specific isotope analysis. Day 35 tissue RNA was sequenced on a NovaSeq S4 Flowcell. Results: Although PAM levels in the liver reflected levels of dietary PAM, PAM was maintained in total and individual brain phospholipid fractions across diet groups at all timepoints. Tissue δ13C-PAM was enriched overall and augmented in mice fed low PAM, compared to medium and high PAM suggesting that DNL from dietary sugars maintained the majority of the brain PAM pool. Furthermore, DNL pathways were upregulated in mice fed low compared to high PAM in the liver, but not the brain at day 35. Conclusions: Lipogenesis from dietary sugars maintains the majority of brain PAM during development and is augmented in mice fed low PAM from birth. Importantly, hepatic lipogenesis from dietary sugars determines PAM availability to the developing brain when low in the diet – a compensatory mechanism identified to maintain total brain PAM pools compared to periphery which ultimately suggests an importance of brain PAM regulation during development.
2023-11-08 | GSE225568 | GEO
Project description:The accumulation of lipid is a histological and biochemical hallmark of obesity-associated hepato-steatosis.Moreover, growing evidenceindicatesthathigher free fatty acids (FFAs) level in hepatocytes affects a myriad of biological processes leading to excessive metabolic imbalance, increased reactive oxygen species (ROS), deregulated autophagy, and impairment of mitochondrial and ER stress, that collectively drives cell death. Lipotoxicity and cell death mechanisms have been studied for many years. However, the molecular signals that link these two events during lipid stress remain poorly understood. From the very beginning, to systematically study hepato-lipotoxicity, HepG2 treated with PA providentially recapitulates the global lipotoxic responses, including insulin resistance to hepatocyte death. Therefore, using this cell-based model system, we pursued a comprehensive, differential quantitative approach where measurements of protein dynamics are analysed by mass spectrometry. Given that indispensable information, successive temporal phosphoproteomics dynamics are allowed us to in-depth analysis of lipotoxicity associated mechanistic network of cell death more precisely.
2022-07-16 | PXD029010 | Pride
Project description:The accumulation of lipid is a histological and biochemical hallmark of obesity-associated hepato-steatosis.Moreover, growing evidenceindicatesthathigher free fatty acids (FFAs) level in hepatocytes affects a myriad of biological processes leading to excessive metabolic imbalance, increased reactive oxygen species (ROS), deregulated autophagy, and impairment of mitochondrial and ER stress, that collectively drives cell death. Lipotoxicity and cell death mechanisms have been studied for many years. However, the molecular signals that link these two events during lipid stress remain poorly understood. From the very beginning, to systematically study hepato-lipotoxicity, HepG2 treated with PA providentially recapitulates the global lipotoxic responses, including insulin resistance to hepatocyte death. Therefore, using this cell-based model system, we pursued a comprehensive, differential quantitative approach where measurements of protein dynamics are analysed by mass spectrometry. Given that indispensable information, successive temporal phosphoproteomics dynamics are allowed us to in-depth analysis of lipotoxicity associated mechanistic network of cell death more precisely.
2022-07-16 | PXD029016 | Pride
Project description:The accumulation of lipid is a histological and biochemical hallmark of obesity-associated hepato-steatosis.Moreover, growing evidenceindicatesthathigher free fatty acids (FFAs) level in hepatocytes affects a myriad of biological processes leading to excessive metabolic imbalance, increased reactive oxygen species (ROS), deregulated autophagy, and impairment of mitochondrial and ER stress, that collectively drives cell death. Lipotoxicity and cell death mechanisms have been studied for many years. However, the molecular signals that link these two events during lipid stress remain poorly understood. From the very beginning, to systematically study hepato-lipotoxicity, HepG2 treated with PA providentially recapitulates the global lipotoxic responses, including insulin resistance to hepatocyte death. Therefore, using this cell-based model system, we pursued a comprehensive, differential quantitative approach where measurements of protein dynamics are analysed by mass spectrometry. Given that indispensable information, successive temporal phosphoproteomics dynamics are allowed us to in-depth analysis of lipotoxicity associated mechanistic network of cell death more precisely.
2022-07-16 | PXD029005 | Pride
Project description:Chronic intake of a high-fat diet increases saturated fatty acids in the brain causing the progression of neurodegenerative diseases. Palmitic acid is a free fatty acid abundant in the diet that at high concentrations may penetrate the blood brain barrier and stimulate the production of pro-inflammatory cytokines, leading to inflammation in astrocytes. The use of the synthetic neurosteroid tibolone in protection against fatty acid toxicity is emerging, but its transcriptional effects on palmitic acid induced lipotoxicity remain unclear. Herein, we performed a transcriptome profiling of normal human astrocytes to investigate the molecular mechanisms by which palmitic acid causes cellular damage to astrocytes, and whether tibolone could reverse its detrimental effects. Astrocytes undergo a profound transcriptional change at 2 mM palmitic acid, affecting the expression of 739 genes, 366 upregulated and 373 downregulated. However, tibolone at 10 nM does not entirely reverse palmitic acid effects. Additionally, the protein protein interaction reveals two novel gene clustering modules. The first module involves astrocyte defense responses by upregulation of pathways associated with antiviral innate immunity, and the second is linked to lipid metabolism. Our data suggest that activation of viral response signaling pathways might be so far, the initial molecular mechanism of astrocytes in response to a lipotoxic insult by palmitic acid, triggered particularly upon increased expression levels of *IFIT2*, *IRF1*, and *XAF1*. Therefore, this novel approach using a global gene expression analysis may shed light on the pleiotropic effects of palmitic acid on astrocytes, and provide a basis for future studies addressed to elucidate these responses in neurodegenerative conditions, which is highly valuable for the design of therapeutic strategies.
2021-02-10 | GSE166500 | GEO
Project description: Not available
| S-EPMC6916734 | biostudies-literature
Project description: Not available
| S-EPMC5473841 | biostudies-literature