The PKR/JNK signalling pathway promotes the palmitic acid-induced myocardial ageing phenotype via SIRT1 inactivation
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE227798 | GEO | 2025/03/01
REPOSITORIES: GEO
Similar Datasets
Project description:Transcriptional regulation of genes in AML12 cells treated with Palmitic acid, LXR lingand (GW3965) and Ulk1 siRNA shows differential effect of Ulk1 KD on LXr responsive genes AML-12 cells co-treated with 0.75mM PA+/- 10µM GW3965 for 24 h +/- Ulk1 SiRNA
2016-03-31 | E-GEOD-74059 | biostudies-arrayexpress
Project description:Metastasis is promoted by fatty acid (FA) uptake and metabolism1-2. How this works, or whether all dietary FAs are prometastatic, is not known. Here we show that dietary palmitic acid (PA), but not oleic acid (OA) or linoleic acid, promotes metastasis, indicating specificity of action for distinct FAs. Strikingly, tumours acutely exposed to a PA–rich diet remain highly metastatic even when serially transplanted. This PA–induced prometastatic memory requires the FA transporter CD36 as well as the epigenetically stable deposition of histone H3 lysine 4 trimethylation by the methyltransferase Set1A/COMPASS. Genes with this metastatic memory predominantly relate to a neural signature that stimulates intratumor oligodendrogenesis and perineural invasion, two parameters strongly correlated with metastasis but etiologically poorly understood3-4. Mechanistically, induction of the epigenetic neural signature and its associated long-term boost in metastasis downstream of PA require the transcription factor EGR2 and the oligodendrocyte-stimulating peptide galanin. We provide evidence for a long-term epigenetic stimulation of metastasis by a dietary metabolite related to tumor innervation. In addition to underscoring the potential danger of eating large amounts of PA (and perhaps other saturated fats), our results reveal novel epigenetic and neural-related therapeutic strategies for metastasis.
2021-11-16 | GSE148318 | GEO
Project description:Metastasis is promoted by fatty acid (FA) uptake and metabolism1-2. How this works, or whether all dietary FAs are prometastatic, is not known. Here we show that dietary palmitic acid (PA), but not oleic acid (OA) or linoleic acid, promotes metastasis, indicating specificity of action for distinct FAs. Strikingly, tumours acutely exposed to a PA–rich diet remain highly metastatic even when serially transplanted. This PA–induced prometastatic memory requires the FA transporter CD36 as well as the epigenetically stable deposition of histone H3 lysine 4 trimethylation by the methyltransferase Set1A/COMPASS. Genes with this metastatic memory predominantly relate to a neural signature that stimulates intratumor oligodendrogenesis and perineural invasion, two parameters strongly correlated with metastasis but etiologically poorly understood3-4. Mechanistically, induction of the epigenetic neural signature and its associated long-term boost in metastasis downstream of PA require the transcription factor EGR2 and the oligodendrocyte-stimulating peptide galanin. We provide evidence for a long-term epigenetic stimulation of metastasis by a dietary metabolite related to tumor innervation. In addition to underscoring the potential danger of eating large amounts of PA (and perhaps other saturated fats), our results reveal novel epigenetic and neural-related therapeutic strategies for metastasis.
2021-11-16 | GSE148319 | GEO
Project description:Metastasis is promoted by fatty acid (FA) uptake and metabolism1-2. How this works, or whether all dietary FAs are prometastatic, is not known. Here we show that dietary palmitic acid (PA), but not oleic acid (OA) or linoleic acid, promotes metastasis, indicating specificity of action for distinct FAs. Strikingly, tumours acutely exposed to a PA–rich diet remain highly metastatic even when serially transplanted. This PA–induced prometastatic memory requires the FA transporter CD36 as well as the epigenetically stable deposition of histone H3 lysine 4 trimethylation by the methyltransferase Set1A/COMPASS. Genes with this metastatic memory predominantly relate to a neural signature that stimulates intratumor oligodendrogenesis and perineural invasion, two parameters strongly correlated with metastasis but etiologically poorly understood3-4. Mechanistically, induction of the epigenetic neural signature and its associated long-term boost in metastasis downstream of PA require the transcription factor EGR2 and the oligodendrocyte-stimulating peptide galanin. We provide evidence for a long-term epigenetic stimulation of metastasis by a dietary metabolite related to tumor innervation. In addition to underscoring the potential danger of eating large amounts of PA (and perhaps other saturated fats), our results reveal novel epigenetic and neural-related therapeutic strategies for metastasis.
2021-11-16 | GSE148320 | GEO
Project description:Metastasis is promoted by fatty acid (FA) uptake and metabolism1-2. How this works, or whether all dietary FAs are prometastatic, is not known. Here we show that dietary palmitic acid (PA), but not oleic acid (OA) or linoleic acid, promotes metastasis, indicating specificity of action for distinct FAs. Strikingly, tumours acutely exposed to a PA–rich diet remain highly metastatic even when serially transplanted. This PA–induced prometastatic memory requires the FA transporter CD36 as well as the epigenetically stable deposition of histone H3 lysine 4 trimethylation by the methyltransferase Set1A/COMPASS. Genes with this metastatic memory predominantly relate to a neural signature that stimulates intratumor oligodendrogenesis and perineural invasion, two parameters strongly correlated with metastasis but etiologically poorly understood3-4. Mechanistically, induction of the epigenetic neural signature and its associated long-term boost in metastasis downstream of PA require the transcription factor EGR2 and the oligodendrocyte-stimulating peptide galanin. We provide evidence for a long-term epigenetic stimulation of metastasis by a dietary metabolite related to tumor innervation. In addition to underscoring the potential danger of eating large amounts of PA (and perhaps other saturated fats), our results reveal novel epigenetic and neural-related therapeutic strategies for metastasis.
2021-11-16 | GSE148317 | GEO
Project description:Metastasis is promoted by fatty acid (FA) uptake and metabolism 1-2 . How this works, or whether all dietary FAs are prometastatic, is not known. Here we show that dietary palmitic acid (PA), but not oleic acid (OA) or linoleic acid, promotes metastasis in oral carcinomas and melanoma, indicating specificity of action for distinct FAs. Strikingly, tumours acutely exposed to a PA–rich diet remain highly metastatic even when serially transplanted. This PA–induced prometastatic memory requires the FA transporter CD36 as well as the epigenetically stable deposition of histone H3 lysine 4 trimethylation by the methyltransferase Set1A/COMPASS. Bulk, single cell and positional RNA sequencing indicate that genes with this metastatic memory predominantly relate to a neural signature that stimulates activation of intratumor Schwann cells and perineural invasion, two parameters strongly correlated with metastasis but etiologically poorly understood 3-4 . Mechanistically, tumour-associated Schwann cells secrete a specialized pro-regenerative extracellular matrix reminiscent of perineuronal nets, which when ablated strongly inhibits metastatic colonization. The induction of the epigenetic neural signature and its associated long-term boost in metastasis downstream of PA require the transcription factor EGR2 and the glial cell-stimulating peptide galanin. We provide evidence for a long-term epigenetic stimulation of metastasis by a dietary metabolite related to a pro-regenerative state of tumour-activated Schwann cells. In addition to underscoring the potential danger of eating large amounts of PA, our results reveal novel epigenetic and neural-related therapeutic strategies for metastasis.
2021-11-16 | GSE182867 | GEO
Project description:This study investigated the cellular response of human periodontal ligament stem cells (PDLSCs) to elevated levels of a specific fatty acid (FA), namely, palmitic acid (PA) and the role of long noncoding RNAs (lncRNAs) in regulating PA exposure-compromised osteogenic potential of PDLSCs. It was found that exposure of PDLSCs to abundant PA led to decreased osteogenic differentiation of cells. Through microarray analysis and gain/loss-of-function studies, AC018926.2 was identified and validated as the lncRNA that was most sensitive to PA and a regulator in the process of PDLSC osteogenic differentiation under a PA condition. Then, RNA sequencing and KEGG analysis demonstrated that AC018926.2 upregulated integrin α2 (ITGA2) expression at the transcriptional level and therefore activated ITGA2/FAK/AKT signaling. Further functional studies revealed that inactivation of ITGA2/FAK/AKT signaling by silencing ITGA2 counteracted the enhancement of the PDLSC osteogenic potential induced by AC018926.2 overexpression. Moreover, the results of bioinformatics analysis and the RNA immunoprecipitation (RIP) assay suggested that AC018926.2 might transcriptionally regulate ITGA2 expression by binding to poly (ADP-ribose) polymerase 1 (PARP1). Our data suggest that AC018926.2 plays a crucial role in PA exposure-compromised osteogenic potential of PDLSCs.
2022-11-26 | GSE218434 | GEO
Project description:The effects of the consumption of high-fat diets (HFD) have been studied to unravel the molecular pathways they are altering in order to understand the link between increased caloric intake, metabolic diseases, and the risk of cognitive dysfunction. The saturated fatty acid, palmitic acid (PA), is the main component of HFD and it has been found increased in the circulation of obese and diabetic people. In the central nervous system, PA has been associated with inflammatory responses in astrocytes, but the effects on neurons exposed to PA have not been largely investigated. Given that PA affect a variety of metabolic pathways, we aimed to analyze the genomic profile activated by this fatty acid to shed light on the mechanisms of neuronal dysfunction. In the current study, we profiled the transcriptome response after PA exposition at non-toxic doses in primary hippocampal neurons. Gene ontology and Reactome analysis revealed a pattern of gene expression which is associated with inflammatory pathways and, importantly, with the activation of lipid metabolism that is considered not very active in neurons. Validation by qRT-PCR of Hmgcs2, Angptl4, Ugt8 and Rnf145 confirmed the results obtained by RNAseq. Overall, these findings suggest that neurons are able to respond to saturated fatty acids changing the expression pattern of genes associated with inflammatory response and lipid utilization that may be involved in the neuronal damage associated with metabolic diseases
2022-03-01 | GSE166985 | GEO
Project description:Saturated fatty acids (SFA) are widely thought to induce inflammation in adipose tissue (AT), while monounsaturated fatty acids (MUFA) are purported to have the opposite effect; however, it is unclear if individual SFA and MUFA behave similarly. Our goal was to examine adipocyte transcriptional networks regulated by individual SFA (palmitic acid, PA; stearic acid, SA) and MUFA (palmitoleic acid, PMA; oleic acid, OA). Global gene expression was examined in differentiated preadipocytes treated with either 250 M-NM-<M PA, SA, PMA, or OA for 48 hrs. Individual fatty acid treatments had significant effects on adipocyte gene expression. Functional analyses revealed that PA induced the TLR signalling pathway, while PMA had the opposite effect. SA and OA had similar effects, with increases in key metabolic pathways including mTOR and PPAR signalling, and a reduction in TLR signalling. Ccl5 was validated as a candidate gene that may mediate the differential inflammatory effects of SFA and MUFA in AT. Individual SFA and MUFA trigger distinct transcriptional responses in differentiated preadipocytes, with inflammatory and metabolic pathways particularly sensitive to these fatty acids. A total of 4 microarrays were run for each FA treatment. We experienced difficulties with the cRNA amplification for one replicate from the OA treated cells; therefore this treatment group only had an n=3. For each sample, 100 ng of total RNA was prepared for hybridization to Affymetrix Mouse Gene 1.1 ST array strips, according to the manufacturerM-bM-^@M-^Ys instructions (Affymetrix Inc., Fremont, CA, USA).
2012-11-13 | E-GEOD-42220 | biostudies-arrayexpress
Project description:Saturated fatty acids (SFA) are widely thought to induce inflammation in adipose tissue (AT), while monounsaturated fatty acids (MUFA) are purported to have the opposite effect; however, it is unclear if individual SFA and MUFA behave similarly. Our goal was to examine adipocyte transcriptional networks regulated by individual SFA (palmitic acid, PA; stearic acid, SA) and MUFA (palmitoleic acid, PMA; oleic acid, OA). Global gene expression was examined in differentiated preadipocytes treated with either 250 μM PA, SA, PMA, or OA for 48 hrs. Individual fatty acid treatments had significant effects on adipocyte gene expression. Functional analyses revealed that PA induced the TLR signalling pathway, while PMA had the opposite effect. SA and OA had similar effects, with increases in key metabolic pathways including mTOR and PPAR signalling, and a reduction in TLR signalling. Ccl5 was validated as a candidate gene that may mediate the differential inflammatory effects of SFA and MUFA in AT. Individual SFA and MUFA trigger distinct transcriptional responses in differentiated preadipocytes, with inflammatory and metabolic pathways particularly sensitive to these fatty acids.
2012-11-13 | GSE42220 | GEO