Impact of inducing hypercholesterolemia on Kupffer cells
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ABSTRACT:
PROVIDER: PRJEB59614 | ENA |
REPOSITORIES: ENA
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Project description:Kupffer cells (KCs) are the largest tissue resident macrophage population in direct contact with blood and thus with circulating lipoproteins. How KCs homeostasis is affected by the build-up of cholesterol-rich lipoproteins in the context of hypercholesterolemia has been poorly investigated. In this study, 5-month-old LDL receptor deficient (C57BL6J background) male mice were subjected to chow diet or a cholesterol-rich (HC) diet for four days to induce hypercholesterolemia. RNA sequencing was then performed on cell sorted KCs.
2024-09-05 | E-MTAB-12611 | biostudies-arrayexpress
Project description:Kupffer cells (KCs) are the tissue resident macrophage population of the liver. With this experiment, we sought to investigate the potential consequences of decreasing embryonically-derived KC numbers on liver gene expression in the context of hypercholesterolemia. 3-month-old CD207-DTR x LDL-receptor deficient (C57BL6J background) female mice were injected with diphtheria toxin (DT) or heat-inactivated DT. Mice were then fed a cholesterol-rich diet to induce hypercholesterolemia. RNA sequencing was performed on liver RNA samples after 4 weeks of diet.
2024-09-05 | E-MTAB-12744 | biostudies-arrayexpress
Project description:Apolipoprotein-B (APOB)-containing lipoproteins cause atherosclerosis. Whether the vasculature is initially responding site, or if atherogenic-dyslipidemia affects other organs simultaneously, is unknown. Here we show that the liver responds to a dyslipidemic insult based on inducible models of familial hypercholesterolemia and APOB tracing. An acute transition to atherogenic APOB-lipoprotein levels resulted in uptake by Kupffer cells and rapid accumulation of triglycerides and cholesterol in the liver. Bulk and single-cell RNA-seq revealed an Kupffer cell-specific transcriptional program that was not activated by a high-fat diet alone, or detected in standard liver function or pathological assays, even in the presence of fulminant atherosclerosis. Depletion of Kupffer cells altered the dynamic of plasma and liver lipid concentrations, indicating that these liver macrophages help restrain and buffer atherogenic lipoproteins, whilst simultaneously secreting atherosclerosis-modulating factors into plasma. Our results place Kupffer cells as key sentinels in organizing systemic responses to lipoproteins at the initiation of atherosclerosis.
2024-02-05 | GSE254879 | GEO
Project description:Apolipoprotein-B (APOB)-containing lipoproteins cause atherosclerosis. Whether the vasculature is initially responding site, or if atherogenic-dyslipidemia affects other organs simultaneously, is unknown. Here we show that the liver responds to a dyslipidemic insult based on inducible models of familial hypercholesterolemia and APOB tracing. An acute transition to atherogenic APOB-lipoprotein levels resulted in uptake by Kupffer cells and rapid accumulation of triglycerides and cholesterol in the liver. Bulk and single-cell RNA-seq revealed an Kupffer cell-specific transcriptional program that was not activated by a high-fat diet alone, or detected in standard liver function or pathological assays, even in the presence of fulminant atherosclerosis. Depletion of Kupffer cells altered the dynamic of plasma and liver lipid concentrations, indicating that these liver macrophages help restrain and buffer atherogenic lipoproteins, whilst simultaneously secreting atherosclerosis-modulating factors into plasma. Our results place Kupffer cells as key sentinels in organizing systemic responses to lipoproteins at the initiation of atherosclerosis.
2024-02-05 | GSE254971 | GEO
Project description:RNAseq of Kupffer cells treated with IL2 and purifed Kupffer cells sub-populations (Kupffer Cell 1 and Kupffer Cell 2)
| PRJNA638642 | ENA
Project description:Kupffer cells have been implicated in the pathogenesis of various liver diseases. However, their involvement in metabolic disorders of the liver, including fatty liver disease, remains unclear. The present study sought to determine the impact of Kupffer cells on hepatic triglyceride storage and to explore the possible mechanisms involved. To that end, C57Bl/6 mice rendered obese and steatotic by chronic high-fat feeding were treated for 1 week with clodronate liposomes, which cause depletion of Kupffer cells. Loss of expression of marker genes Cd68, F4/80, and Clec4f, and loss of Cd68 immunostaining verified almost complete removal of Kupffer cells from the liver. Also, expression of complement components C1, the chemokine (C-C motif) ligand 6 (Ccl6), and cytokines interleukin-15 (IL-15) and IL-1beta were markedly reduced. Importantly, Kupffer cell depletion significantly decreased liver triglyceride and glucosylceramide levels concurrent with increased expression of genes involved in fatty acid oxidation including peroxisome proliferator-activated receptor alpha (PPARalpha), carnitine palmitoyltransferase 1A (Cpt1alpha), and fatty acid transport protein 2 (Fatp2). Treatment of mice with IL-1beta decreased expression of PPARalpha and its target genes, which was confirmed in primary hepatocytes. Consistent with these data, IL-1beta suppressed human and mouse PPARalpha promoter activity. Suppression of PPARalpha promoter activity was recapitulated by overexpression of nuclear factor kappaB (NF-kappaB) subunit p50 and p65, and was abolished upon deletion of putative NF-kappaB binding sites. Finally, IL-1beta and NF-kappaB interfered with the ability of PPARalpha to activate gene transcription. CONCLUSION: Our data point toward important cross-talk between Kupffer cells and hepatocytes in the regulation of hepatic triglyceride storage. The effect of Kupffer cells on liver triglycerides are at least partially mediated by IL-1beta, which suppresses PPARalpha expression and activity. Expression profiling of livers from mice fed control, low-fat diet diet or high-fat diet for 20weeks with or without knockdown of Kupffer cells.
2011-10-17 | E-GEOD-33044 | biostudies-arrayexpress
Project description:We used transcriptomics to identify vascular gene expression profiles of high-fat-fed Tibetan minipig induced-hypercholesterolemia and atherosclerotic models, to verify the hypothesis that hypercholesterolemia induces innate and adaptive immune responses to accelerate atherosclerosis. Results showed that hypercholesterolemia and atherosclerosis models occurred in the high-fat fed minipigs at 8 and 24 weeks. GSEA analysis showed that the changes of hypercholesterolemia accelerated atherosclerosis were focused on immunity inflammation and lipid metabolism, immune cells such as NK cells and T cells participated in the biological processes. 4 significant modules of 344 overlapping DEGs were identified by STEM analysis. 6 hub genes (ITGB2, TYROBP, LCP2, PTPRC, C5AR1, and PTPN6) and two immune-related pathways (Natural killer cell-mediated cytotoxicity and T cell receptor signaling pathway) were identified by CytoHubba plugin and KEGG analysis. Correlation analysis showed that hub genes were significantly correlated with lipid deposition, IMT, WBC, CD4, and CD8, which was consistent with RT-PCR validation results. From above, this study reveals that hypercholesterolemia accelerate atherosclerosis progression by inducing innate and adaptive immune responses.
2020-03-30 | GSE140412 | GEO
Project description:To reveal the transcriptomes associated with M1 or M2-polarized Kupffer cells, the primary Kupffer cells isolated from mouse liver were treated with lipopolysaccharides or IL-4 and the gene expression patterns were analyzed by microarray. To study the role of RORα in Kupffer cell polarization, Kupffer cells were treated with RORα ligands and transcriptions were compared with those of the M1/M2 polarized Kupffer cells.
2016-09-03 | GSE86397 | GEO
Project description:Impact of embryonically-derived Kupffer cells depletion on liver gene expression under hypercholesterolemic conditions
| PRJEB60456 | ENA
Project description:To reveal the transcriptomes associated with Maresin 1-treated Kupffer cells, the primary Kupffer cells isolated from mouse liver were treated with maresin 1 and the gene expression patterns were analyzed by microarray.
2019-04-03 | GSE122430 | GEO