Liver microRNA transcriptome reveals miR-182 as link between type 2 diabetes and fatty liver disease in obesity
Ontology highlight
ABSTRACT:
ORGANISM(S): synthetic construct Homo sapiens
PROVIDER: GSE176025 | GEO | 2023/10/31
REPOSITORIES: GEO
Similar Datasets
Project description:Although the global prevalence of obesity and type 2 diabetes is rising, the molecular mechanisms of dysregulated glucose and lipid metabolism are still incompletely understood. Epigenetic mechanisms were shown to have an impact in disease manifestation, but the underlying hepatic miRNA expression signature is not completely elucidated. We used microarrays to perform a comprehensive screen of the complete microRNA transcriptome in liver samples of diet induced obese (DIO) mice in order to identify expressed microRNAs that might target genes of hepatic lipid and glucose metabolism.
2023-10-31 | GSE211367 | GEO
Project description:Mediator complex function as an integrative hub for transcriptional regulation. Here we show that Mediator subunit MED23 regulate glucose and lipid metabolism via FOXO1 in liver. Here, we have generated a liver-specific Med23-knockout (LMKO) mouse and found that Med23-deletion in liver improved glucose and lipid metabolism, as well as insulin responsiveness, and prevented diet-induced obesity. Mechanistically, MED23 participated in gluconeogenesis and cholesterol synthesis by interacting with FOXO1. Disruption of this interaction by hepatic Med23-deletion impaired the Mediator and RNAP II recruitment and partially reduced the expression of the FOXO1 target genes. Remarkably, acute hepatic Med23 knockdown in db/db mice significantly improved insulin sensitivity. Overall, our data revealed Mediator MED23 as a critical regulator of glucose and lipid metabolism, suggesting novel therapeutic strategies against metabolic diseases.
2015-03-16 | GSE48966 | GEO
Project description:Impaired hepatic glucose and lipid metabolism are hallmarks of type–2 diabetes. Increased sulfide production or sulfide–donor compounds may beneficially regulate hepatic metabolism. Disposal of sulfide through the sulfide oxidation pathway (SOP) is critical for maintaining sulfide within a safe physiological range. We show that mice lacking the liver–enriched mitochondrial SOP enzyme thiosulfate sulfur–transferase (Tst—/— mice) exhibit high circulating sulfide, increased gluconeogenesis, hypertriglyceridemia and fatty liver. Unexpectedly, hepatic sulfide levels are normal in Tst—/— mice due to exaggerated induction of sulfide disposal, with an associated suppression of global protein persulfidation and nuclear respiratory factor–2 target protein levels. Hepatic proteomic and persulfidomic profiles converge on gluconeogenesis and lipid metabolism, revealing a selective deficit in medium–chain fatty acid oxidation in Tst—/— mice. We reveal a critical role for TST in hepatic metabolism that has implications for sulfide-donor strategies in the context of metabolic disease.
2021-11-11 | PXD028909 | Pride
Project description:Purpose: MetS consist of five risk factors: elevated blood pressure and fasting glucose, visceral obesity, dyslipidemia and hypercholesterinemia. The physiological impact of lipid metabolism indicated as visceral obesity and hepatic lipid accumulation is still under debate. One major cause of disturbed lipid metabolism might be dysfunction of cellular organelles controlling energy homeostasis, i.e. mitochondria and peroxisomes. Experimental design: The New Zealand Obese (NZO) mouse model exhibits a polygenic syndrome of obesity, insulin resistance, triglyceridemia and hypercholesterolemia that resembles human metabolic syndrome. We applied a combinatorial approach of lipidomics with liver transcriptomics, 2D-DIGETM and mass spectroscopy based organelle proteomics of highly purified mitochondria and peroxisomes in male mice, to investigate molecular mechanisms related to the impact of lipid metabolism in the pathophysiology of the metabolic syndrome. Conclusions and clinical relevance: Proteome analyses of liver organelles indicated differences in fatty acid metabolism, oxidative stress and response, mainly influenced by PG-C1α/PPARα mediated pathways. These results were in accordance with serum lipid profiles and elevated organelle functionality. These data emphasize that metabolic syndrome is accompanied with increased mitochondria and peroxisomal activity controlling directly cellular energy homeostasis to cope with dyslipidemia and hypercholesterinemia driven hepatic lipid overflow in developing a fatty liver.
2017-11-01 | GSE95489 | GEO
Project description:Alcohol’s impairment of both hepatic lipid metabolism and insulin resistance (IR) are key drivers of alcoholic steatosis, the initial stage of alcoholic liver disease (ALD). Pharmacologic reduction of lipotoxic ceramide prevents alcoholic steatosis and glucose intolerance in mice, but potential off-target effects limit its strategic utility. Here, we employed a hepatic-specific acid-ceramidase (ASAH) overexpression model to reduce hepatic ceramides in a Lieber-DeCarli model of experimental alcoholic steatosis. We examined effects of alcohol on hepatic lipid metabolism, body composition, energy homeostasis and insulin sensitivity as measured by hyperinsulinemic-euglycemic clamp. Our results demonstrate that hepatic ceramide reduction ameliorates the effects of alcohol on hepatic lipid droplet accumulation by promoting VLDL secretion and lipophagy, the latter of which involves ceramide cross-talk between the lysosomal and lipid droplet compartments. We additionally demonstrate that hepatic ceramide reduction prevents alcohol’s inhibition of hepatic insulin signaling. These effects on the liver are associated with a reduction in oxidative stress markers and are relevant to humans, as we observe peri-lipid droplet ASAH expression in human ALD. Together, our results suggest a potential role for hepatic ceramide inhibition in preventing ALD.
2020-07-08 | GSE139015 | GEO
Project description:Analysis of glucose and Lipid metabolism in male and female offspring after protein restriction of the mother Male offspring showed features of metabolic syndrome after receiving a high fat diet, regardless of the diet of the dam. Glucose and lipid metabolism in male offspring was unaltered. Insulin sensitivity and hepatic fatty acid storage in female offspring of low-protein-fed dams changed in such a way that it resembled the male pattern of insulin sensitivity and hepatic fatty acid storage. Microarray analysis on hepatic gene expression patterns confirmed these findings. We therefore conclude that in mice, maternal protein restriction does not change the response of glucose and fatty acid metabolism to a high fat diet in male offspring, but does program metabolism in female offspring in such a way that it resembles male metabolism. Our findings might have implications for potential future gender-specific treatment of the features of metabolic diseases. Total RNA obtained from liver (16 samples per gender) were compared in the different groups. In total, 4 groups per gender, each group consisting of 4 biological replicates.
2012-02-08 | E-GEOD-15940 | biostudies-arrayexpress
Project description:We have previously shown that paramylon (PM) supplementation to a high fat diet reduces the postprandial glucose rise, serum total and LDL-cholesterol, and abdominal fat accumulation in mice; however, the mechanism has not been determined. We evaluated the potential mechanism in male C57BL/6J mice fed a high-fat diet supplemented with 5% PM powder, extracted from Eu-glena gracilis, for 12 weeks. Abdominal fat weight, and serum lipids were measured; ileal and hepatic mRNA expression were assessed using DNA microarray and real-time PCR. The poten-tial mechanism of PM on modulating lipid metabolism was explored by gene ontology (GO) classification and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Dietary supplementation with PM resulted in decreased abdominal fat accumulation and serum LDL-cholesterol concentrations via suppression of the digestion and absorption pathway in the ileum and activation of the hepatic PPAR signaling pathway. Improvement in glucose tolerance may be the result of lipid metabolism modification because the glucose metabolism pathway was not detected by GO classification and KEGG pathway analysis. PM intake also directly enhanced immunoglobulin production.
2021-08-04 | GSE181289 | GEO
Project description:Analysis of glucose and Lipid metabolism in male and female offspring after protein restriction of the mother Male offspring showed features of metabolic syndrome after receiving a high fat diet, regardless of the diet of the dam. Glucose and lipid metabolism in male offspring was unaltered. Insulin sensitivity and hepatic fatty acid storage in female offspring of low-protein-fed dams changed in such a way that it resembled the male pattern of insulin sensitivity and hepatic fatty acid storage. Microarray analysis on hepatic gene expression patterns confirmed these findings. We therefore conclude that in mice, maternal protein restriction does not change the response of glucose and fatty acid metabolism to a high fat diet in male offspring, but does program metabolism in female offspring in such a way that it resembles male metabolism. Our findings might have implications for potential future gender-specific treatment of the features of metabolic diseases.
2012-02-08 | GSE15940 | GEO
Project description:This SuperSeries is composed of the following subset Series:; GSE8290: Comprehensive analysis of PPARα-dependent regulation of hepatic lipid metabolism by expression profiling - 1; GSE8291: Comprehensive analysis of PPARα-dependent regulation of hepatic lipid metabolism by expression profiling - 2; GSE8292: Comprehensive analysis of PPARα-dependent regulation of hepatic lipid metabolism by expression profiling - 3; GSE8295: Comprehensive analysis of PPARα-dependent regulation of hepatic lipid metabolism by expression profiling - 4; GSE8302: Comprehensive analysis of PPARα-dependent regulation of hepatic lipid metabolism by expression profiling - 5; PPARalpha is a ligand-activated transcription factor involved in the regulation of nutrient metabolism and inflammation. Although much is already known about the function of PPARalpha in hepatic lipid metabolism, many PPARalpha-dependent pathways and genes have yet to be discovered. In order to obtain an overview of PPARalpha-regulated genes relevant to lipid metabolism, and to probe for novel candidate PPARalpha target genes, livers from several animal studies in which PPARalpha was activated and/or disabled were analyzed by Affymetrix GeneChips. Numerous novel PPARalpha-regulated genes relevant to lipid metabolism were identified. Out of this set of genes, eight genes were singled out for study of PPARalpha-dependent regulation in mouse liver and in mouse, rat, and human primary hepatocytes, including thioredoxin interacting protein (Txnip), electron-transferring-flavoprotein beta polypeptide (Etfb), electron-transferring-flavoprotein dehydrogenase (Etfdh), phosphatidylcholine transfer protein (Pctp), endothelial lipase (EL, Lipg), adipose triglyceride lipase (Pnpla2), hormone-sensitive lipase (HSL, Lipe), and monoglyceride lipase (Mgll). Using an in silico screening approach, one or more PPAR response elements (PPREs) were identified in each of these genes. Regulation of Pnpla2, Lipe, and Mgll, which are involved in triglyceride hydrolysis, was studied under conditions of elevated hepatic lipids. In wild-type mice fed a high fat diet, the decrease in hepatic lipids following treatment with the PPARalpha agonist Wy14643 was paralleled by significant up-regulation of Pnpla2, Lipe, and Mgll, suggesting that induction of triglyceride hydrolysis may contribute to the anti-steatotic role of PPARalpha. Our study illustrates the power of transcriptional profiling to uncover novel PPARalpha-regulated genes and pathways in liver. Experiment Overall Design: Refer to individual Series
2008-06-16 | E-GEOD-8316 | biostudies-arrayexpress
Project description:Adiponectin regulates expression of hepatic genes critical for glucose and lipid metabolism.
| PRJNA167280 | ENA