Rat gut metagenome
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA806362 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
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| SRR17999639.fastq.gz | Fastqsanger.gz |
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Project description:Purpose: While various functions of peripheral serotonin are known, the direct role of serotonin in regulating hepatic lipid metabolism in vivo is not well understood. We studied whether serotonin directly acts on liver to regulate lipid metabolism. Methods: Methods: 12 weeks aged liver-specific Htr2a KO (Albumin-Cre+/-; Htr2aflox/flox, herein named Htr2a LKO) mice and wildtype (WT) littermates were fed a high-fat diet (HFD, 60% fat calories) for 8 weeks. Results: Hepatic lipid droplet accumulation, NAFLD activity score, and hepatic triglyceride levels were dramatically reduced in HFD-fed Htr2a LKO mice compared to WT littermates. Conclusions: Gut-derived serotonin is a direct regulator of hepatic lipid metabolism via a gut TPH1-liver HTR2A endocrine axis. And shows promise as a novel drug target to ameliorate NAFLD with minimal systemic metabolic effects.
2018-11-27 | GSE120662 | GEO
Project description:The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is associated with abnormalities of liver lipid metabolism, especially with the accumulation of saturated fatty acids (FA). On the contrary, a diet enriched with n-3 polyunsaturated FA (n-3-PUFA) has been reported to ameliorate the progression of NAFLD. The aim of our study was to investigate the impact of dietary n-3-PUFA enrichment on the development of NAFLD and liver lipidome. Mice were fed for 6 weeks either high-fat methionine choline-deficient diet (MCD) or standard chow (two groups fed MCD, two control groups, both with or without n-3-PUFA). Genome-wide transcriptome analysis of liver tissue was performed and revealed differences in liver mRNA transcriptomes after MCD as well as n-3-PUFA administration.
2023-12-14 | E-MTAB-13399 | biostudies-arrayexpress
Project description:Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of lipid droplets (LD) in hepatocytes. NAFLD development and progression is associated with an increase in hepatic cholesterol and decreased autophagy and lipophagy flux. Previous studies have shown that the expression of lysosomal acid lipase (gene=LIPA, protein=LAL), which can hydrolyze both triglyceride and cholesteryl esters, is inversely correlated with the severity of NAFLD. In addition, ablation of LAL activity results in profound NAFLD. Based on this, we predicted that overexpressing LIPA in the livers of mice fed a Western diet (FPC) would prevent the development of NAFLD. As expected, mice fed the FPC diet exhibited numerous markers of NAFLD including hepatomegaly, lipid accumulation, and inflammation. Unexpectedly, LAL overexpression did not attenuate steatosis and had only minor effects on neutral lipid composition. However, LAL overexpression exacerbated inflammatory gene expression and infiltration of immune cells in mice fed the FPC diet. LAL overexpression also resulted in abnormal phagosome accumulation and lysosomal lipid accumulation depending upon the dietary treatment. Hepatic overexpression of LAL drove immune cell infiltration and inflammation and did not attenuate the development of NAFLD suggesting that targeting LAL expression is not a viable route to treat NAFLD.
2021-11-03 | GSE180377 | GEO
Project description:Major causes of lipid accumulation in liver are increased import, synthesis or decreased catabolism of fatty acids. The latter is caused by dysfunction of cellular organelle controlling energy homeostasis, i.e. mitochondria. However, peroxisomes appear to be an important organelle in lipid metabolism of hepatocytes, but little is known about their role in the development of non-alcoholic fatty liver disease (NAFLD). To investigate the role of peroxisomes next to mitochondria in excessive hepatic lipid accumulation we used the leptin resistant db/db mice on C57BLKS background, a mouse model that develops hyperphagia induced diabetes with obesity and NAFLD. We used microarrays to determine differences in hepatic gene expression in a mouse model for NAFDL (BKS.Cg-Leprdb (db/db)) and their wildtype littermates C57BL/KSlepr+/+ (BKS) to determine the effect of persistent hepatic lipid accumulation.
2015-03-23 | GSE59930 | GEO
Project description:Nuclear receptors (NRs) play a crucial role in non-alcoholic fatty liver disease (NAFLD) and have been widely studied(Tran et al. 2018). However, the underlying mechanisms of NR regulation remain largely unclear. Here, we show that miR-20b plays a key role in modulating PPARα, a master regulator of nutrient metabolism and energy homeostasis in the pathogenesis of fatty liver(Wahli et al. 1995; Dongiovanni and Valenti 2013). Using network analysis and RNA-seq to determine the correlation between NRs and microRNA in NAFLD patients, we revealed that miR-20b directly targets PPARα. The expression of miR-20b was remarkably upregulated in free fatty acid (FA)-treated hepatocytes and the livers of both obesity-induced mice and NAFLD patients. Overexpression of miR-20b dramatically increased hepatic lipid accumulation and plasma triglyceride levels. Furthermore, miR-20b significantly reduced fatty acid oxidation and mitochondrial biogenesis by directly targeting PPARα. Fenofibrate, a specific agonist of PPARα, lost its ability to ameliorate hepatic steatosis in miR-20b-introduced mice. Finally, inhibition of miR-20b dramatically increased FA oxidation and uptake, resulting in improved insulin sensitivity and a decrease in NAFLD progression. Taken together, these results demonstrate that the novel miR-20b directly targets PPARα, plays a significant role in hepatic lipid metabolism, and presents an opportunity for the development of novel therapeutics for NAFLD.
2021-03-09 | GSE168484 | GEO
Project description:Obesity and associated increased prevalence of non-alcoholic fatty liver (NAFLD) disease is suggested to be positively modulated by a high protein (HP) diet in humans and rodents. The aim was to detect mechanisms by which a HP diet prevents hepatic lipid accumulation by means of transcriptomics. To study the acute and long term effect of a high protein ingestion on hepatic lipid accumulation under both low and high fat (HF) conditions, mice were fed combinations of high (35%) or low (10%) fat and high (50%) or normal (15%) protein diets for 1 or 12 weeks. Body composition, liver fat, VLDL production rate and gene expression were investigated. Differences in metabolic processes and functions in the liver were identified using gene set enrichment analysis on microarray data. Mice fed the HP diets developed less adiposity and decreased hepatic lipid accumulation due a combination of induced processes mainly involved in protein catabolism such as transamination, TCA cycle and oxidative phosphorylation. Feeding a HP diet can successfully prevent the development of NAFLD by using ingested energy for oxidation instead of storage. Wild type mice were fed combinations of high (35%) or low (10%) fat and high (50%) or normal (15%) protein diets for 1 or 12 weeks. After the diet intervention period, the animals were killed and liver tissue was removed. Total RNA was isolated, pooled and subjected to gene expression profiling.
2012-11-21 | E-GEOD-37897 | biostudies-arrayexpress
Project description:Patients with non-alcoholic fatty liver disease (NAFLD), especially advanced non-alcoholic steatohepatitis (NASH), have an increased risk of cardiovascular diseases (CVD) due to the production of pro-inflammatory factors, vasoactive and thrombogenic molecules, or insulin resistance and related disorders. While elevated risk and incidence of CVD events in NAFLD/NASH are well established, whether such events will, in turn, influence the pathogenesis of NAFLD remains unknown. Here, we show that myocardial infarction (MI) accelerates the linear hepatic pathological progression of NAFLD. In humans, NAFLD patients who experienced CVD events after their diagnosis of NAFLD show a rapid progression of hepatic fibrosis. In mouse models of NASH, MI promotes hepatic fibrosis, accompanied by elevated circulating Ly6Chi monocytes and their recruitment to the damaged liver tissues. Depleting these cells abrogate MI-induced hepatic pathological effects in mice with NASH. Meanwhile, MI substantially elevates circulating and cardiac periostin contents, which act on hepatocytes and stellate cells to promote hepatic lipid accumulation and fibrosis, finally exacerbating hepatic pathological progression of NASH. Additionally, specific silence of cardiac periostin markedly attenuates MI-induced hepatic pathological progression of mice with NASH. These preclinical and clinical results demonstrate that MI alternates systemic homeostasis and upregulates the production of pro-fibrotic factors, triggering cross-disease communication that accelerates hepatic pathological progression of NAFLD.
2024-06-04 | GSE254698 | GEO
Project description:Non-alcoholic fatty liver disease (NAFLD) involves hepatic accumulation of intracellular lipid droplets via incompletely understood processes. Here, we report distinct and cooperative NAFLD roles of LysTTT-5’tRF transfer RNA fragments and microRNA miR-194-5p. Unlike lean animals, dietary-induced NAFLD mice showed concurrent hepatic decrease of both LysTTT-5’tRF and miR-194-5p levels, which were restored following miR-132 antisense oligonucleotide treatment which suppresses hepatic steatosis. Moreover, exposing human-derived Hep G2 cells to oleic acid for 7 days co-suppressed miR-194-5p and LysTTT-5’tRF levels while increasing lipid accumulation. Importantly, transfecting fattened cells with a synthetic LysTTT-5’tRF mimic elevated mRNA levels of the metabolic regulator β-Klotho while decreasing triglyceride amounts by 30% within 24 hours. In contradistinction, antisense suppression of miR-194-5p induced accumulation of its novel target, the NAFLD-implicated lipid droplet-coating PLIN2 protein. Further, two out of 15 steatosis-alleviating screened drug-repurposing compounds, Danazol and Latanoprost, elevated miR-194-5p or LysTTT-5’tRF levels. The different yet complementary roles of miR-194-5p and LysTTT-5’tRF offer new insights into the complex roles of small non-coding RNAs and the multiple pathways involved in NAFLD pathogenesis.
2024-01-31 | GSE248320 | GEO
Project description:Non-alcoholic fatty liver disease (NAFLD) involves hepatic accumulation of intracellular lipid droplets via incompletely understood processes. Here, we report distinct and cooperative NAFLD roles of LysTTT-5’tRF transfer RNA fragments and microRNA miR-194-5p. Unlike lean animals, dietary-induced NAFLD mice showed concurrent hepatic decrease of both LysTTT-5’tRF and miR-194-5p levels, which were restored following miR-132 antisense oligonucleotide treatment which suppresses hepatic steatosis. Moreover, exposing human-derived Hep G2 cells to oleic acid for 7 days co-suppressed miR-194-5p and LysTTT-5’tRF levels while increasing lipid accumulation. Importantly, transfecting fattened cells with a synthetic LysTTT-5’tRF mimic elevated mRNA levels of the metabolic regulator β-Klotho while decreasing triglyceride amounts by 30% within 24 hours. In contradistinction, antisense suppression of miR-194-5p induced accumulation of its novel target, the NAFLD-implicated lipid droplet-coating PLIN2 protein. Further, two out of 15 steatosis-alleviating screened drug-repurposing compounds, Danazol and Latanoprost, elevated miR-194-5p or LysTTT-5’tRF levels. The different yet complementary roles of miR-194-5p and LysTTT-5’tRF offer new insights into the complex roles of small non-coding RNAs and the multiple pathways involved in NAFLD pathogenesis.
2024-01-31 | GSE248319 | GEO
Project description:Non-alcoholic fatty liver disease (NAFLD) involves hepatic accumulation of intracellular lipid droplets via incompletely understood processes. Here, we report distinct and cooperative NAFLD roles of LysTTT-5’tRF transfer RNA fragments and microRNA miR-194-5p. Unlike lean animals, dietary-induced NAFLD mice showed concurrent hepatic decrease of both LysTTT-5’tRF and miR-194-5p levels, which were restored following miR-132 antisense oligonucleotide treatment which suppresses hepatic steatosis. Moreover, exposing human-derived Hep G2 cells to oleic acid for 7 days co-suppressed miR-194-5p and LysTTT-5’tRF levels while increasing lipid accumulation. Importantly, transfecting fattened cells with a synthetic LysTTT-5’tRF mimic elevated mRNA levels of the metabolic regulator β-Klotho while decreasing triglyceride amounts by 30% within 24 hours. In contradistinction, antisense suppression of miR-194-5p induced accumulation of its novel target, the NAFLD-implicated lipid droplet-coating PLIN2 protein. Further, two out of 15 steatosis-alleviating screened drug-repurposing compounds, Danazol and Latanoprost, elevated miR-194-5p or LysTTT-5’tRF levels. The different yet complementary roles of miR-194-5p and LysTTT-5’tRF offer new insights into the complex roles of small non-coding RNAs and the multiple pathways involved in NAFLD pathogenesis.
2024-01-31 | GSE248317 | GEO