Arachidonoyl-taurine protects from diet-induced hepatic steatosis and inflammation
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE292568 | GEO | 2026/05/12
REPOSITORIES: GEO
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Project description:Metabolic dysfunction-associated steatotic liver disease and its progressive and inflamma-tory form metabolic dysfunction-associated steatohepatitis represents a global health challenge, with limited treatment options available. In this study we identified an endoge-nous, understudied omega-6 fatty acid metabolite, arachidonoyl-taurine (ARA-T), capable of mitigating liver disease. ARA-T levels increased in human plasma of chronic and acute fatty liver and their abundance can be driven in humans and mice by dietary supplementa-tion of arachidonic acid. Surprisingly, our genetic model of elevated circulating ARA-T levels prevented inflammation and hepatic steatosis by increased uptake and turnover of fatty ac-ids in the liver. Pharmacological administration of ARA-T reduced liver weight and diet-induced hepatic lipid deposition in mice, demonstrating its potential to protect against and reverse the progression of liver disease. Thus, ARA-T may represent a way to protect against pro-inflammatory actions of omega-6 fatty acids thereby contributing to regulation of in-flammation and accumulation of hepatic lipids.
2026-05-21 | PXD061361 | Pride
Project description:Metabolic dysfunction-associated steatotic liver disease and its progressive and inflamma-tory form metabolic dysfunction-associated steatohepatitis represents a global health challenge, with limited treatment options available. In this study we identified an endoge-nous, understudied omega-6 fatty acid metabolite, arachidonoyl-taurine (ARA-T), capable of mitigating liver disease. ARA-T levels increased in human plasma of chronic and acute fatty liver and their abundance can be driven in humans and mice by dietary supplementa-tion of arachidonic acid. Surprisingly, our genetic model of elevated circulating ARA-T levels prevented inflammation and hepatic steatosis by increased uptake and turnover of fatty ac-ids in the liver. Pharmacological administration of ARA-T reduced liver weight and diet-induced hepatic lipid deposition in mice, demonstrating its potential to protect against and reverse the progression of liver disease. Thus, ARA-T may represent a way to protect against pro-inflammatory actions of omega-6 fatty acids thereby contributing to regulation of in-flammation and accumulation of hepatic lipids.
2026-05-20 | PXD075585 | Pride
Project description:Metabolic dysfunction-associated steatotic liver disease and its progressive and inflamma-tory form metabolic dysfunction-associated steatohepatitis represents a global health challenge, with limited treatment options available. In this study we identified an endoge-nous, understudied omega-6 fatty acid metabolite, arachidonoyl-taurine (ARA-T), capable of mitigating liver disease. ARA-T levels increased in human plasma of chronic and acute fatty liver and their abundance can be driven in humans and mice by dietary supplementa-tion of arachidonic acid. Surprisingly, our genetic model of elevated circulating ARA-T levels prevented inflammation and hepatic steatosis by increased uptake and turnover of fatty ac-ids in the liver. Pharmacological administration of ARA-T reduced liver weight and diet-induced hepatic lipid deposition in mice, demonstrating its potential to protect against and reverse the progression of liver disease. Thus, ARA-T may represent a way to protect against pro-inflammatory actions of omega-6 fatty acids thereby contributing to regulation of in-flammation and accumulation of hepatic lipids.
2026-05-20 | PXD075440 | Pride
Project description:Identification of the effect of transgenerationnal supplementation with omega 3 fatty acids on the resistance to a diet induced obesity challenge Although several lines of evidence suggested that omega 3 fatty acids (FA) may protect from obesity and its related disorders by modulation of the metabolism of insulin-responsive organs, the long term effect remains unknown. Preservation of the liver metabolic homeostasis could be a key mediator of omega 3 FA effects. The impact of transgenerational intake of long chain omega 3 PUFA on hepatic adaptations during a nutritional challenge was investigated in young C57Bl6J male mice.
2020-11-01 | GSE145620 | GEO
Project description:The optimal ratio of omega-6 to omega-3 polyunsaturated fatty acids (PUFAs) is important for keeping homeostasis of biological processes and metabolism, yet the underlying biological mechanism is poorly understood. The objective of this study was to identify changes in the pig liver transcriptome induced by a diet enriched with omega-6 and omega-3 fatty acids, and to characterize the biological mechanisms related to PUFA metabolism. Polish Landrace pigs (n =12) were fed diet enriched with linoleic acid (LA, omega-6) and alpha-linolenic acid (ALA, omega-3 family) or standard diet as a control. The fatty acids profiling was assayed in order to verify how feeding influenced the fatty acids content in liver, and subsequently next-generation sequencing (NGS) was used to identify differentially expressed genes (DEG) between transcriptomes between dietary groups. The biological mechanisms and pathway interaction networks were identified by analysis in DAVID and Cytoscape tools. Fatty acids profile analysis indicated a higher contribution of PUFAs in liver for LA and ALA-enriched diet group, particularly for the omega-3 fatty acids family, but not omega-6. Next-generation sequencing identified 3,565 DEG, 1,484 of which were induced and 2,081 were suppressed by PUFA supplemenation. Low ratio of omega-6/-3 fatty acids resulted in modulation of fatty acids metabolism pathways and over-representation of genes involved in membrane composition, signal transduction and immune response pathways. In conclusion, a diet enriched with omega-6 and omega-3 fatty acids altered the transcriptomic profile of the pig liver and affected a set of genes involved in metabolic pathways important to animal health status. Hepatic mRNA profiles of Polish Landrace pig breed fed two different diets, were generated by deep sequencing, using Illumina MiSeq. Experimental diet was enriched with polyunsaturated fatty acids (omega-6 and omega-3), while standard diet remain as a cotrol. 2 pooled samples each containing RNA extracts from 6 individuals livers were analyzed.
2016-03-15 | E-GEOD-72123 | biostudies-arrayexpress
Project description:Background/purpose Periodontal diseases exacerbate hepatic inflammation and diseases like non-alcoholic fatty liver disease via circulating pathogenic factors from periodontal tissue. Long-term pre-symptomatic state eventually leads to the development of such hepatic diseases. However, it is uncertain if periodontitis contributes in the onset of hepatic pre-symptomatic state. Herein, we conducted a hepatic whole transcription analysis of periodontitis-affected mice and healthy mice to understand the early functional changes in the hepatic system in periodontitis-affected mice. Materials and methods Silk ligatures were tied around mice second maxillary molars for 14 days to develop periodontitis. RNA-seq samples were collected from periodontal tissues and liver tissues of mice with periodontitis and healthy mice. Lipidomic analysis of hepatic omega-3 fatty acids in periodontitis-affected and healthy mice was conducted. The anti-inflammatory effects of omega-3 fatty acids and their metabolites were elucidated using hepatocytes HepG2 cells. Results In the liver of mice with periodontitis, genes coding for cytochrome P450 such as Cyp4a12a and Cyp4a12b were identified as significantly down-regulated genes. Lipidomic analyses identified that epoxidation and subsequent hydrolysis of hepatic omega-3 fatty acids were inhibited in periodontitis-affected mice. Eicosapentaenoic acid metabolites, epoxy eicosatetraenoic acid and dihydroxyeicosatetraenoic acid, inhibited inflammatory responses of HepG2 cells. Conclusion These results suggest that, in the liver of periodontitis-affected mice, due to the reduced activity of omega-3 fatty acid epoxidation, pre-symptomatic state with pro-inflammatory status develop. Therefore, early intervention of periodontitis might contribute to the prevention of the onset of hepatic diseases.
2024-05-03 | GSE264546 | GEO
Project description:The mechanisms underlying the progression of non-alcoholic steatohepatitis (NASH) are not completely elucidated. In this study we have integrated gene expression profiling of liver biopsies of NASH patients with translational studies in a mouse model of steatohepatitis and with pharmacological interventions in isolated hepatocytes to identify a novel mechanism implicated in the pathogenesis of NASH. By using high-density oligonucleotide microarray analysis we identified a significant enrichment of known genes involved in the multi-step catalysis of long chain polyunsaturated fatty acids, including delta-5 and 6 desaturases. A combined inhibitor of delta-5 and delta-6 desaturases significantly reduced intracellular lipid accumulation and inflammatory gene expression in isolated hepatocytes. Gas chromatography analysis revealed impaired delta-5 desaturase activity toward the omega-3 pathway in livers from mice with high-fat diet (HFD)-induced NASH. Consistently, restoration of omega-3 index in transgenic fat-1 mice expressing an omega-3 desaturase, which allows the endogenous conversion of omega-6 into omega-3 fatty acids, produced a significant reduction in hepatic insulin resistance, hepatic steatosis, macrophage infiltration and necroinflammatory liver injury, accompanied by attenuated expression of genes involved in inflammation, fatty acid uptake and lipogenesis. These results were comparable to those obtained in a group of mice receiving a HFD supplemented with EPA/DHA. Of interest, hepatocytes from fat-1 mice or supplemented with EPA exhibited synergistic anti-steatotic and anti-inflammatory actions with the delta-5/ delta-6 inhibitor. Conclusion: These findings indicate that both endogenous and exogenous restoration of the hepatic balance between omega-6 and omega-3 fatty acids and/or modulation of desaturase activities exert preventive actions in NASH. The complete database comprised the expression measurements of 18185 genes for liver sample groups: 8 non-alcoholic steatohepatitis (NASH ) and 7 control samples. This dataset is part of the TransQST collection.
2013-04-02 | E-GEOD-37031 | biostudies-arrayexpress
Project description:The optimal ratio of omega-6 to omega-3 polyunsaturated fatty acids (PUFAs) is important for keeping homeostasis of biological processes and metabolism, yet the underlying biological mechanism is poorly understood. The objective of this study was to identify changes in the pig liver transcriptome induced by a diet enriched with omega-6 and omega-3 fatty acids, and to characterize the biological mechanisms related to PUFA metabolism. Polish Landrace pigs (n =12) were fed diet enriched with linoleic acid (LA, omega-6) and alpha-linolenic acid (ALA, omega-3 family) or standard diet as a control. The fatty acids profiling was assayed in order to verify how feeding influenced the fatty acids content in liver, and subsequently next-generation sequencing (NGS) was used to identify differentially expressed genes (DEG) between transcriptomes between dietary groups. The biological mechanisms and pathway interaction networks were identified by analysis in DAVID and Cytoscape tools. Fatty acids profile analysis indicated a higher contribution of PUFAs in liver for LA and ALA-enriched diet group, particularly for the omega-3 fatty acids family, but not omega-6. Next-generation sequencing identified 3,565 DEG, 1,484 of which were induced and 2,081 were suppressed by PUFA supplemenation. Low ratio of omega-6/-3 fatty acids resulted in modulation of fatty acids metabolism pathways and over-representation of genes involved in membrane composition, signal transduction and immune response pathways. In conclusion, a diet enriched with omega-6 and omega-3 fatty acids altered the transcriptomic profile of the pig liver and affected a set of genes involved in metabolic pathways important to animal health status.
2016-03-15 | GSE72123 | GEO
Project description:The mechanisms underlying the progression of non-alcoholic steatohepatitis (NASH) are not completely elucidated. In this study we have integrated gene expression profiling of liver biopsies of NASH patients with translational studies in a mouse model of steatohepatitis and with pharmacological interventions in isolated hepatocytes to identify a novel mechanism implicated in the pathogenesis of NASH. By using high-density oligonucleotide microarray analysis we identified a significant enrichment of known genes involved in the multi-step catalysis of long chain polyunsaturated fatty acids, including delta-5 and 6 desaturases. A combined inhibitor of delta-5 and delta-6 desaturases significantly reduced intracellular lipid accumulation and inflammatory gene expression in isolated hepatocytes. Gas chromatography analysis revealed impaired delta-5 desaturase activity toward the omega-3 pathway in livers from mice with high-fat diet (HFD)-induced NASH. Consistently, restoration of omega-3 index in transgenic fat-1 mice expressing an omega-3 desaturase, which allows the endogenous conversion of omega-6 into omega-3 fatty acids, produced a significant reduction in hepatic insulin resistance, hepatic steatosis, macrophage infiltration and necroinflammatory liver injury, accompanied by attenuated expression of genes involved in inflammation, fatty acid uptake and lipogenesis. These results were comparable to those obtained in a group of mice receiving a HFD supplemented with EPA/DHA. Of interest, hepatocytes from fat-1 mice or supplemented with EPA exhibited synergistic anti-steatotic and anti-inflammatory actions with the delta-5/ delta-6 inhibitor. Conclusion: These findings indicate that both endogenous and exogenous restoration of the hepatic balance between omega-6 and omega-3 fatty acids and/or modulation of desaturase activities exert preventive actions in NASH.
2013-04-02 | GSE37031 | 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