RNA-seq of hiPSCs-derived hepatocytes cultured in 3D and treated with oleic or palmitic acid
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PROVIDER: PRJEB45771 | ENA |
REPOSITORIES: ENA
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Project description:We aimed to develop an in vitro system that would recapitulate the key features of Non-Alcoholic Fatty Liver Disease (NAFLD). We took advantage of human pluripotent stem cells (hIPSCs) to establish 3D cultures of hIPSCs-derived hepatocytes to study NAFLD pathogenesis in vitro. Cultures were challenged with free fatty acid to mimic NAFLD, and transcriptomic analyses were used to confirm the presence of a NAFLD signature.
2023-10-01 | E-MTAB-10598 | biostudies-arrayexpress
Project description:Through scRNA-sequencing of primary human hepatocytes (PHHs), we have identified four subgroups of hepatocytes. A phenotyping 5-probe cocktail (Sanofi-Aventis) has been used to assess their metabolic capacity. Upon cocktail treatment, the characterized four hepatocyte subgroups displayed differential gene expression profiles and exhibited xenobiotic metabolism-related specialization. Intracellular lipid accumulation achieved through loading the cells with free fatty acids (FFA, 2:1 oleic:palmitic acid), differently affected the four subgroups. Moreover, we have shown that intracellular fat accumulation diminishes the drug-related metabolic capacity of hepatocytes.
2023-09-19 | E-MTAB-11530 | biostudies-arrayexpress
Project description:Unlike other saturated fatty acids, dietary stearic acid does not appear to raise plasma cholesterol. The reason for this remains to be established, although it appears that it must be related to inherent differences in the metabolism of the fatty acid. In the present study, we have looked at the metabolism of palmitic acid and stearic acid, in comparison with oleic acid, by cultured hamster hepatocytes. Stearic acid was taken up more slowly and was poorly incorporated into both cellular and secreted triacylglycerol. Despite this, stearic acid stimulated the synthesis and secretion of triacylglycerol to the same extent as the other fatty acids. Incorporation into cellular phospholipid was lower for oleic acid than for palmitic acid and stearic acid. Desaturation of stearic acid, to monounsaturated fatty acid, was found to be greater than that of palmitic acid. Oleic acid produced from stearic acid was incorporated into both triacylglycerol and phospholipid, representing 13% and 6% respectively of the total after a 4 h incubation. Significant proportions of all of the fatty acids were oxidized, primarily to form ketone bodies, but by 8 h more oleic acid had been oxidized compared with palmitic acid and stearic acid.
| S-EPMC1217427 | biostudies-other
Project description:A1AT deficiency is an autosomal not recessive disorder caused by mutations in the SERPINA1 gene. Individuals with the Z variant retain polymerised protein in the endoplasmic reticulum of hepatocytes, predisposing them to liver disease. This study primarily aimed to uncover the molecular mechanisms that link protein misfolding to liver injury. To that end, RNA was extracted from hepatocytes differentiated from hIPSCs carrying the Z variant and mutation-corrected hIPSCs (control). The second objective of the study was to benchmark the gene expression profile of both hIPSC-derived hepatocytes types to primary hepatocytes of wild type and a Z variant A1AT genotype.
2018-06-26 | E-MTAB-6781 | biostudies-arrayexpress
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: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
Project description:Compared to ordinary rapeseed, high-oleic acid rapeseed has higher levels of monounsaturated fatty acids and lower levels of saturated fatty acid and polyunsaturated fatty acids, and thus is of high nutritional and health value. In addition, high-oleic acid rapeseed oil imparts cardiovascular protective effects. Based on these properties, high-oleic acid oil crops have been extensively investigated and cultivated. In this study, we employed a microarray analysis with high oleic acid line and low oleic acid line from the developing seeds (27 days after flowering) of Brassica napus.
2018-09-20 | GSE120223 | GEO
Project description:Primary human hepatocytes were treated with compounds modulating steatosis: palmitic acid, compound C and metformin qPCR miRNA expression profiling. Hepatocytes were treated as indicated in the summary. Equal amount total RNA was pooled prior to miRNA expression analysis
2020-02-11 | GSE145039 | GEO
Project description:Brassica napus high oleic acid vs. low oleic acid
| PRJNA492174 | ENA