The effect of palmitate on gene expression profile in proliferating myoblasts
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE75378 | GEO | 2015/11/25
SECONDARY ACCESSION(S): PRJNA304026
REPOSITORIES: GEO
Similar Datasets
Project description:High-fat diet or exposure to saturated fatty acids affects skeletal muscle growth and function. The aim of the present study was to investigate the effect of palmitate on the transcriptomic profile of mouse C2C12 myoblasts. Global gene expression was evaluated using whole mouse genome oligonucleotide microarrays, and the results were validated through real-time PCR. A total of 4047genes were identified as differentially expressed, including 3492 down-regulated and 555 up-regulated genes during 48-h-exposure to palmitate (0.1 mmol/l). Functional classification showed the involvement of PA-regulated genes in several processes which regulate cell growth. In conclusion, palmitate modifies the expression of genes associated with: i) myoblast responsiveness to hormones and growth factors, ii) cytokine and growth factor expression, and iii) regulation of cell-cell cell-matrix communication. Such alterations can affect myoblast growth and differentiation, however further studies in this field are required. To whom the correspondence should be addressed: Dr K. Grzelkowska-Kowalczyk; e-mail: k_grzel_kow@poczta.fm, tel/fax: (48 22) 847 24 52 After scanning of hybridized microarrays, quantitation of slide images was performed using Feature Extraction Software (Agilent) using default parameters and the raw data were exported to GeneSpring GX 12 (Agilent, Santa Clara, CA) and log2 transformed. For identification of genes significantly altered in cell compared with the control normal gene set. Total detected entities were filtered by flags (detected, non detected) and error (coefficient of variation: CV < 50.0 percent) to remove very low signal entities and to select reproducible signal values of entities among the replicated experiments, respectively. In statistical analysis, separated for experiment with myoblasts treated with palmitate acid was used t-test unpaired (p < 0.05) with multiple testing correction: Benjamini-Hochberg <0.05, all significant changes over fold change 1.6 were selected.
2015-11-25 | E-GEOD-75378 | biostudies-arrayexpress
Project description:The purpose of the study was to investigate the effect of IFN-γ on transcriptomic profile of differentiating mouse C2C12 myogenic cells. Global gene expression was evaluated using the oligonucleotide whole mouse genome microarrays and was validated with real-time PCR method. Exogenous IFN-γ (1 ng/ml) increased myoblast proliferation, but decreased cell viability, the fusion index and the cellular content of myosin heavy chain, MyHC in C2C12 cultures on the 3rd day of differentiation. IFN-γ up-regulated genes were mainly involved in biological processes such as: cell cycle, regulation of cell proliferation, programmed cell death, inflammatory, vasculature development, regulation of cytokine, transmembrane receptor protein tyrosine kinase signaling pathway, and chemotaxis, whereas down-regulated genes contributed mainly to: regulation of transcription, cell-cell signaling, nitrogen compound biosynthetic process, transmembrane receptor protein ser/thr protein kinase signaling pathway, and regulation of Wnt receptor signaling pathway. IFN-γ up-regulated the expression of cytokines/growth factors controlling cell proliferation (Cxcl10, Il15, Ccl2, Fgf7, Figf, Csf1, Vegfc, Hgf). Moreover, IFN-γ: i) down-regulated genes encoding factors that are anabolic for muscle cells (Fst, Igf-1); ii) inhibited pro-myogenic transcription (via Mef2a, Nfkb1, and Pparg); iii) decreased expression of genes controlling cell adhesion and sarcolemma/cytoskeleton organization; and iv) activated the proteolytic pathways: proteasomes and catepsins, leading to protein degradation and impaired myotube growth. Our data suggest that the effect of IFN-γ on mygenesis is, at least partly, associated with the regulation of muscle cell secretom at the transcriptional level. To whom the correspondence should be addressed: Dr K. Grzelkowska-Kowalczyk; e-mail: k_grzel_kow@poczta.fm, tel/fax: (48 22) 847 24 52
2014-02-05 | GSE53392 | GEO
Project description:The purpose of the study was to investigate the effect of IFN-M-NM-3 on transcriptomic profile of differentiating mouse C2C12 myogenic cells. Global gene expression was evaluated using the oligonucleotide whole mouse genome microarrays and was validated with real-time PCR method. Exogenous IFN-M-NM-3 (1 ng/ml) increased myoblast proliferation, but decreased cell viability, the fusion index and the cellular content of myosin heavy chain, MyHC in C2C12 cultures on the 3rd day of differentiation. IFN-M-NM-3 up-regulated genes were mainly involved in biological processes such as: cell cycle, regulation of cell proliferation, programmed cell death, inflammatory, vasculature development, regulation of cytokine, transmembrane receptor protein tyrosine kinase signaling pathway, and chemotaxis, whereas down-regulated genes contributed mainly to: regulation of transcription, cell-cell signaling, nitrogen compound biosynthetic process, transmembrane receptor protein ser/thr protein kinase signaling pathway, and regulation of Wnt receptor signaling pathway. IFN-M-NM-3 up-regulated the expression of cytokines/growth factors controlling cell proliferation (Cxcl10, Il15, Ccl2, Fgf7, Figf, Csf1, Vegfc, Hgf). Moreover, IFN-M-NM-3: i) down-regulated genes encoding factors that are anabolic for muscle cells (Fst, Igf-1); ii) inhibited pro-myogenic transcription (via Mef2a, Nfkb1, and Pparg); iii) decreased expression of genes controlling cell adhesion and sarcolemma/cytoskeleton organization; and iv) activated the proteolytic pathways: proteasomes and catepsins, leading to protein degradation and impaired myotube growth. Our data suggest that the effect of IFN-M-NM-3 on mygenesis is, at least partly, associated with the regulation of muscle cell secretom at the transcriptional level. To whom the correspondence should be addressed: Dr K. Grzelkowska-Kowalczyk; e-mail: k_grzel_kow@poczta.fm, tel/fax: (48 22) 847 24 52 After scanning of hybridized microarrays, quantitation of slide images was performed using Feature Extraction Software (Agilent) using default parameters and the raw data were exported to GeneSpring GX 12 (Agilent, Santa Clara, CA) and log2 transformed. For identification of genes significantly altered in cell compared with the control normal gene set, total detected entities were filtered by flags (present, marginal) to remove very low signal entities and to select reproducible signal values of entities among the replicated experiments, respectively. In statistical analysis, separated for experiment with myoblasts treated with IFNG (IFNG vs CTRL 1-4) was used t-test unpaired (p < 0.05) with multiple testing correction: Benjamini-Hochberg <0.05, all significant changes over fold change 2 were selected. Analysis of GO, GSEA and signaling pathway was carried out using GeneSpring GX 12 (Agilent) and the DAVID Classification System (p<0.05).
2014-02-05 | E-GEOD-53392 | biostudies-arrayexpress
Project description:Cancer cells outgrowing in distant organs of metastasis rewire their metabolism to fuel on the available nutrients. While this is often considered an adaptive pressure limiting metastasis formation, some nutrients available at the metastatic site naturally or through changes in organ physiology may inherently promote metastatic growth. We find that the lung, a frequent site of metastasis, is a lipid-rich environment. Moreover, we observe that pathological conditions such as pre-metastatic niche formation and obesity further increase the availability of the fatty acid palmitate in the lung. We find that targeting palmitate processing inhibits spheroid growth in vitro and metastasis formation in lean and obese mice. Mechanistically, we discover that breast cancer cells use palmitate to synthesize acetyl-CoA in a carnitine palmitoyltransferase 1a (CPT1a)-dependent manner. Lysine acetyltransferase 2a (KAT2a), whose expression is promoted by palmitate availability, relies on the available acetyl-CoA to acetylate the NF-B subunit p65. This favors nuclear location of p65 and activates a pro-metastatic transcriptional program. Accordingly, deletion of KAT2a phenocopies CPT1a silencing in vitro as well as in vivo and patients with breast cancer show co-expression of both proteins in metastases across palmitate-rich metastatic sites. In conclusion, we find that palmitate-rich environments foster metastasis growth by increasing p65 acetylation resulting in elevated NF-B signaling.
2022-06-01 | GSE196992 | GEO
Project description:Cancer cells outgrowing in distant organs of metastasis rewire their metabolism to fuel on the available nutrients. While this is often considered an adaptive pressure limiting metastasis formation, some nutrients available at the metastatic site naturally or through changes in organ physiology may inherently promote metastatic growth. We find that the lung, a frequent site of metastasis, is a lipid-rich environment. Moreover, we observe that pathological conditions such as pre-metastatic niche formation and obesity further increase the availability of the fatty acid palmitate in the lung. We find that targeting palmitate processing inhibits spheroid growth in vitro and metastasis formation in lean and obese mice. Mechanistically, we discover that breast cancer cells use palmitate to synthesize acetyl-CoA in a carnitine palmitoyltransferase 1a (CPT1a)-dependent manner. Lysine acetyltransferase 2a (KAT2a), whose expression is promoted by palmitate availability, relies on the available acetyl-CoA to acetylate the NF-B subunit p65. This favors nuclear location of p65 and activates a pro-metastatic transcriptional program. Accordingly, deletion of KAT2a phenocopies CPT1a silencing in vitro as well as in vivo and patients with breast cancer show co-expression of both proteins in metastases across palmitate-rich metastatic sites. In conclusion, we find that palmitate-rich environments foster metastasis growth by increasing p65 acetylation resulting in elevated NF-B signaling.
2022-06-01 | GSE196991 | GEO
Project description:Cancer cells outgrowing in distant organs of metastasis rewire their metabolism to fuel on the available nutrients. While this is often considered an adaptive pressure limiting metastasis formation, some nutrients available at the metastatic site naturally or through changes in organ physiology may inherently promote metastatic growth. We find that the lung, a frequent site of metastasis, is a lipid-rich environment. Moreover, we observe that pathological conditions such as pre-metastatic niche formation and obesity further increase the availability of the fatty acid palmitate in the lung. We find that targeting palmitate processing inhibits spheroid growth in vitro and metastasis formation in lean and obese mice. Mechanistically, we discover that breast cancer cells use palmitate to synthesize acetyl-CoA in a carnitine palmitoyltransferase 1a (CPT1a)-dependent manner. Lysine acetyltransferase 2a (KAT2a), whose expression is promoted by palmitate availability, relies on the available acetyl-CoA to acetylate the NF-B subunit p65. This favors nuclear location of p65 and activates a pro-metastatic transcriptional program. Accordingly, deletion of KAT2a phenocopies CPT1a silencing in vitro as well as in vivo and patients with breast cancer show co-expression of both proteins in metastases across palmitate-rich metastatic sites. In conclusion, we find that palmitate-rich environments foster metastasis growth by increasing p65 acetylation resulting in elevated NF-B signaling.
2022-06-01 | GSE197134 | GEO
Project description:Obesity-induced insulin resistance of the liver is characterised by increased gluconeogenesis, which contributes to elevated blood glucose levels in individuals with type 2 diabetes. Research into how fatty acids induce insulin resistance has commonly focused on the induction of insulin resistance. We hypothesise that by shifting focus to the reversal of an insulin resistant phenotype, novel insights can be made into the mechanisms by which insulin resistance can be overcome. Using global gene and lipid expression profiling, we aimed to identify biological pathways altered in parallel with restoration of palmitate-induced deregulation of glucose production using metformin and sodium salicylate. FAO hepatoma cells were treated with palmitate (0.075mM, 48h) with or without metformin (0.25mM) and sodium salicylate (2mM) in the final 24h of palmitate treatment, and effects on glucose production were determined. Microarray followed by gene set enrichment analysis was performed to investigate pathway regulation. A lipidomic analysis (HPLC-MS/MS) and measurement of secreted bile acids and cholesterol were performed. Reversal of palmitate-induced impairment of glucose production by metformin and sodium salicylate was characterised by down-regulated expression of metabolic pathways regulating acetyl-CoA to cholesterol and bile acid biosynthesis. Total levels of intracellular and secreted cholesterol and bile acids were not different between impaired and restored glucose production. Total intracellular levels of diacylgycerol, triacylglycerol and cholesterol esters increased with palmitate (impaired glucose production), however, these were not further altered with metformin and sodium salicylate (restored glucose production). Six individual lipid species containing 18:0 and 18:1 side-chains were reduced by metformin and sodium salicylate. Widespread lipid metabolism changes induced by the reversal of palmitate-induced deregulation of glucose production with metformin and sodium salicylate were identified. While cholesterol and bile acid levels remained unchanged, the flux through these pathways may in part explain these findings. The identification of lipid species containing 18:0 and 18:1 side chains being regulated alongside changes to glucose production may indicate potential mediators of glucose production and insulin resistance. Three-condition experiment, Vehicle, Palmitate (PA) and Palmitate (PA) + Metformin (Met) + Sodium Sailcylate (NaS) with biological replicates: 8 Vehicle, 20 PA and 20 PA+Met+NaS , independently grown and harvested. One replicate per array.
2013-11-08 | E-GEOD-52204 | biostudies-arrayexpress
Project description:Cancer cells outgrowing in distant organs of metastasis rewire their metabolism to fuel on the available nutrients. While this is often considered an adaptive pressure limiting metastasis formation, some nutrients available at the metastatic site naturally or through changes in organ physiology may inherently promote metastatic growth. We find that the lung, a frequent site of metastasis, is a lipid-rich environment. Moreover, we observe that pathological conditions such as pre-metastatic niche formation and obesity further increase the availability of the fatty acid palmitate in the lung. We find that targeting palmitate processing inhibits spheroid growth in vitro and metastasis formation in lean and obese mice. Mechanistically, we discover that breast cancer cells use palmitate to synthesize acetyl-CoA in a carnitine palmitoyltransferase 1a (CPT1a)-dependent manner. Lysine acetyltransferase 2a (KAT2a), whose expression is promoted by palmitate availability, relies on the available acetyl-CoA to acetylate the NF-κB subunit p65. This favors nuclear location of p65 and activates a pro-metastatic transcriptional program. Accordingly, deletion of KAT2a phenocopies CPT1a silencing in vitro as well as in vivo and patients with breast cancer show co-expression of both proteins in metastases across palmitate-rich metastatic sites. In conclusion, we find that palmitate-rich environments foster metastasis growth by increasing p65 acetylation resulting in elevated NF-κB signaling.
2022-10-28 | GSE216695 | GEO
Project description:Palmitate or vehicle control-treated breast cancer cells
2014-07-16 | E-MTAB-2601 | biostudies-arrayexpress
Project description:Obesity-induced insulin resistance of the liver is characterised by increased gluconeogenesis, which contributes to elevated blood glucose levels in individuals with type 2 diabetes. Research into how fatty acids induce insulin resistance has commonly focused on the induction of insulin resistance. We hypothesise that by shifting focus to the reversal of an insulin resistant phenotype, novel insights can be made into the mechanisms by which insulin resistance can be overcome. Using global gene and lipid expression profiling, we aimed to identify biological pathways altered in parallel with restoration of palmitate-induced deregulation of glucose production using metformin and sodium salicylate. FAO hepatoma cells were treated with palmitate (0.075mM, 48h) with or without metformin (0.25mM) and sodium salicylate (2mM) in the final 24h of palmitate treatment, and effects on glucose production were determined. Microarray followed by gene set enrichment analysis was performed to investigate pathway regulation. A lipidomic analysis (HPLC-MS/MS) and measurement of secreted bile acids and cholesterol were performed. Reversal of palmitate-induced impairment of glucose production by metformin and sodium salicylate was characterised by down-regulated expression of metabolic pathways regulating acetyl-CoA to cholesterol and bile acid biosynthesis. Total levels of intracellular and secreted cholesterol and bile acids were not different between impaired and restored glucose production. Total intracellular levels of diacylgycerol, triacylglycerol and cholesterol esters increased with palmitate (impaired glucose production), however, these were not further altered with metformin and sodium salicylate (restored glucose production). Six individual lipid species containing 18:0 and 18:1 side-chains were reduced by metformin and sodium salicylate. Widespread lipid metabolism changes induced by the reversal of palmitate-induced deregulation of glucose production with metformin and sodium salicylate were identified. While cholesterol and bile acid levels remained unchanged, the flux through these pathways may in part explain these findings. The identification of lipid species containing 18:0 and 18:1 side chains being regulated alongside changes to glucose production may indicate potential mediators of glucose production and insulin resistance.
2013-11-08 | GSE52204 | GEO