Saccharomyces cerevisiae
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA350552 | ENA |
REPOSITORIES: ENA
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Project description:Fatty liver is a condition of excessive triglyceride accumulation in hepatocytes. Additionally, hepatocytes showed a high degree of fat droplet accumulation during excessive alcohol consumption and metabolic syndrome. However, the molecular mechanisms involved in fat droplet formation remain unknown. This study used an in vitro fatty liver formation model of the human liver cancer cell line HepG2 to comprehensively search for fat droplet formation-related genes whose expression changes during fat droplet formation. Microarray analysis with extracted total RNA determined the genes that are involved in fat droplet formation and confirmed their expression by real-time polymerase chain reaction after culturing HepG2 cells in a culture medium containing 0, 50, 200, and 500 μM of oleic acid for 24 h. The results revealed 142 genes demonstrating increased expressions by >2.0 fold with oleic acid treatment and 426 genes demonstrating decreased expressions. Perilipin 2 (PLIN2) was estimated as the gene most closely associated with fatty liver. Lipid droplet formation in HepG2 upregulated PLIN2 in an oleic acid-treated concentration-dependent manner. These results indicate the involvement of genes in oleate treatment-induced lipid droplet formation in HepG2, particularly PLIN2 may play an important role.
2023-12-01 | GSE248166 | GEO
Project description:The liver has a high demand for phosphatidylcholine (PC) particularly in overnutrition where reduced phospholipid levels have been implicated in the development of non-alcoholic fatty liver disease (NAFLD). Whether other pathways exist in addition to de novo PC synthesis that contribute to hepatic PC pools remains unknown. Here, we identified the lysophosphatidylcholine (LPC) transporter Mfsd2a as critical for maintaining hepatic phospholipid pools. Hepatic Mfsd2a expression was induced in patients having NAFLD and in mice in response to dietary fat via glucocorticoid receptor action. Mfsd2a liver-specific deficiency in mice (L2aKO) led to a robust NASH-like phenotype within just two weeks of dietary fat challenge associated with reduced hepatic phospholipids containing linoleic acid. Reducing dietary choline intake in L2aKO mice exacerbated liver pathology and deficiency of liver phospholipids containing polyunsaturated fatty acids (PUFA). Treating hepatocytes with LPC containing oleate and linoleate, two abundant blood-derived LPCs, specifically induced lipid droplet biogenesis and contributed to phospholipid pools, while LPC containing the omega-3 fatty acid DHA promoted lipid droplet formation and suppressed lipogenesis. This study revealed that PUFA containing LPCs drive both hepatic lipid droplet formation, suppress lipogenesis and sustain hepatic phospholipid pools--processes that are critical for protecting the liver from excess dietary fat.
2023-07-27 | GSE173545 | GEO
Project description:Palm and coconut oils are linked to cardiovascular disease and diabetes because of their high saturated fatty acid (SFA) content but exactly how exogenous SFAs, but not unsaturated fatty acids (UFA), are toxic to cells remains unknown. In insulin-producing, β-cells of the Islets of Langerhans, loss of which exacerbates diabetes, we found that SFAs but not UFAs were toxic because they disable a highly conserved lipid droplet biogenesis machinery. We show that palmitate (a major SFA of these oils), but not palmitoleic or oleic, S-acylates the highly conserved ER-resident FITM2 protein, required for lipid coalescence and droplet budding from the ER. The S-acylation marks FITM2 for ubiquitination and proteosomal degradation, leaving SFAs within the ER instead safe sequestration within lipid droplets. ER-stress ensues with rapid induction of ER stress leading to β-cell apoptosis. Specific deletion of FITM2 in β-cells disrupts calcium signaling and key β-cell TFs and exacerbates high fat diet-induced ER stress and diabetes. Rescue by overexpression ameliorates ER-stress and β-cell apoptosis thus demonstrating an important link between lipid species and cell ability to sequester them away from the ER in the form of lipid droplets.
2021-07-08 | GSE133939 | GEO
Project description:How hepatocytes respond to a fatty acid stimulus is the topic of continuous research, since it is essential for our understanding of non-alcoholic fatty liver disease a pathology with a hard to detect onset, estimated to be present in a quarter of the adult human population. As advanced stages include cirrhosis and development of hepatocellular carcinoma, early detection and intervention is crucial. To improve our understanding of the development of non-alcoholic fatty liver disease we treated a human hepatoma cell line model, HepG2, with increasing concentrations of common fatty acids namely myristic, palmitic and oleic acid. To reproduce more representative conditions, we also included combinations of these fatty acids and monitored the cellular response with an in-depth proteomics approach and imaging techniques. The two saturated fatty acids presented a similar phenotype of a dose dependent decrease of proliferation rates and little lipid droplet formation. Interestingly, our data corroborated that this drop in proliferation rates was due to delayed cell cycle progression following myristic acid treatment, whereas palmitic acid led to cellular apoptosis. In contrast, oleic acid, as well as saturated fatty acid mixtures with oleic acid, led to a dose dependent increase of lipid droplet volume without the adverse impact on proliferation. Comparing the outcomes from harmful single fatty acid treatments and the well tolerated fatty acid mixes, we were able to differentiate between fatty acid specific cellular responses and likely common lipotoxic denominators. Two of them, A2M and SERPINA3, are modulators of the innate immune system and are likely involved in the inflammation occurring on systemic level. The remaining four include transcription factors like H2AFY, which recently has been proposed as a biomarker for hepatocellular carcinoma. Conclusively, our study not only manages to contextualise proteome alterations following fatty acid treatment, but also highlights differences between cellular effects of two common saturated fatty acids.
2022-04-04 | PXD030764 | Pride
Project description:Deletion of Stat3 induced genes influencing protein metabolism, transport, chemotaxis and apoptosis and decreased the expression of genes mediating lipid synthesis and metabolism. Srebf1 and 2, key regulators of fatty acid and steroid biosynthesis, were decreased in Stat3D/D mice. Stat3 influenced both pro- and anti-apoptotic pathways, regulating and maintaining the balance between a subset of pro- and anti-apoptotic genes that determine cell death or survival. Akt, a known target of Stat3, participates in many Stat3 mediated pathways including Jak-Stat signaling, apoptosis, the MAPK signaling, cholesterol and fatty acid biosynthesis. Deletion of Stat3 from type II epithelial cells altered the expression of genes regulating diverse cellular processes, including cell growth and apoptosis, lipid biosynthesis and metabolism. Stat3 regulates cell formation through a complex regulatory network that likely enhances alveolar epithelial cell survival and surfactant/lipid synthesis, necessary for the protection of the lung during injury. Experiment Overall Design: To better understand the roles and molecular mechanisms by which Stat3 influences gene expression in lung, the effect of cell-selective deletion of Stat3 (Stat3D/D) on genome wide mRNA expression profiles was determined in murine type II alveolar epithelial cells. Differentially expressed genes were identified from Affymetrix Murine GeneChips analysis and subjected to gene ontology classification promoter analysis, pathway mapping and literature mining.
2008-06-15 | E-GEOD-6846 | biostudies-arrayexpress
Project description:Saturated fatty acids promotes β-cell toxicity by disabling intracellular lipid droplet formation through S-acylation of FIT2
| PRJNA553175 | ENA
Project description:Visceral fat (VF) and subcutaneous fat (SF) are developmentally different tissues with different gene expression. Islet-1 (ISL1), a LIM-homeobox transcription factor with important developmental and regulatory function in islet, neural, and cardiac tissue, is virtually absent in SF but substantially expressed in the stromovascular [preadipocyte containing] fraction of VF; expression correlates negatively with adiposity in rodents and man. ISL1 expression is transiently increased in 3T3-L1 preadipocytes during early differentiation, suggesting a functional role. To examine the role of ISL1 in adipogenesis, we tested whether retroviral overexpression of ISL1 in 3T3-L1 preadipocytes affected their ability to differentiate into mature adipocytes. Terminal differentiation was assessed by Oil Red O [lipid droplet] staining and by immunoblot detection of adipocyte marker proteins, including aP2 and GLUT4. ISL1 significantly inhibited lipid droplet formation, reduced lipid accumulation (about 80% inhibition, p<0.05), and substantially inhibited aP2 and GLUT4 expression. ISL1 did not inhibit expression of C/EBPb and C/EBPd after induction of differentiation, but reduced PPARg and C/EBPa by >50% at both mRNA and protein level. In addition, the PPARg agonist, rosiglitazone, substantially rescued ISL1 inhibited adipogenesis in the absence of exogenous PPARg, and fully rescued in the presence of exogenous PPARg. In summary, ISL1 overexpression inhibited fat droplet formation, lipid accumulation, and adipocyte-specific gene expression; there was accompanying inhibition of C/EBPa, PPARg and downstream gene expression. We conclude that ISL1 overexpression inhibited adipocyte differentiation by inhibition of PPARg regulated gene expression. As abdominal obesity strongly correlates with insulin resistance, and cardiovascular risk, ISL1 up-regulation may impact abdominal obesity and its concomitant metabolic derangements. Total cellular RNA was isolated from 3T3-L1 cells expressing Flag-ISL1 or not at 48 h following treatment with differentiation cocktail. Individual RNA from biological triplicates was used for microarray analysis.
2012-09-05 | E-GEOD-40565 | biostudies-arrayexpress
Project description:Some embryos display better survival potential to cryopreservation than others. The cause of such phenotype is still unclear and might be due to cell damage during cryopreservation, resulting from over-accumulation and composition of lipids. In cattle embryos, in vitro culture conditions have been shown to impact the number of lipid droplets within blastomeres. So far, the impact of breed on embryonic lipid content has not yet been studied. In this study were compared the colour, lipid droplet abundance, lipid composition, mitochondrial activity, and gene expression of in vivo collected Jersey breed embryos which are known to display poor performance post-freezing and in vivo Holstein embryos which have good cryotolerance. Holstein in vivo day 6 embryos vs Jersey in vivo day 6 embryos: 4 replicates of each breed, with dye-swap.
2014-10-22 | E-GEOD-62553 | biostudies-arrayexpress
Project description:Deletion of Stat3 induced genes influencing protein metabolism, transport, chemotaxis and apoptosis and decreased the expression of genes mediating lipid synthesis and metabolism. Srebf1 and 2, key regulators of fatty acid and steroid biosynthesis, were decreased in Stat3D/D mice. Stat3 influenced both pro- and anti-apoptotic pathways, regulating and maintaining the balance between a subset of pro- and anti-apoptotic genes that determine cell death or survival. Akt, a known target of Stat3, participates in many Stat3 mediated pathways including Jak-Stat signaling, apoptosis, the MAPK signaling, cholesterol and fatty acid biosynthesis. Deletion of Stat3 from type II epithelial cells altered the expression of genes regulating diverse cellular processes, including cell growth and apoptosis, lipid biosynthesis and metabolism. Stat3 regulates cell formation through a complex regulatory network that likely enhances alveolar epithelial cell survival and surfactant/lipid synthesis, necessary for the protection of the lung during injury. Keywords: genotype comparison
2007-08-24 | GSE6846 | GEO
Project description:We analyzed changes in the protein profiles that occur during differentiation and maturation of cultured human subcutaneous white preadipocytes. We divided the three cell lines (Cell Line-1, Cell Line-2, and Cell Line-3) of Caucasian-derived subcutaneous preadipocytes into five stages: i) subcutaneous preadipocytes as stage-1, ii) after inducing differentiation into adipocytes as stage-2, iii-v) from the initiation of lipid droplet formation to become mature subcutaneous adipocytes was defined as stage-3 to stage-5, depending on lipid droplet amount and formation. Proteins from the cells were extracted at each stage (stage-1 to stage-5), proteolytically cleaved using trypsin, and analyzed using untargeted liquid chromatography and mass spectrometry.
2022-07-04 | PXD035060 | JPOST Repository