Ontology highlight
ABSTRACT:
PROVIDER: PRJNA682774 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Starvation causes the accumulation of lipid droplets in the liver, a somewhat counterintuitive phenomenon that is nevertheless conserved from flies to humans. Much like fatty liver resulting from overfeeding, hepatic lipid accumulation (steatosis) during undernourishment can lead to lipotoxicity and atrophy of the liver. Here, we found that while surface populations of Astyanax mexicanus undergo this evolutionarily conserved response to starvation, the starvation-resistant cavefish larvae of the same species do not display an accumulation of lipid droplets upon starvation. Moreover, cavefish are resistant to liver atrophy during starvation, providing a unique system to explore strategies for liver protection. Using comparative transcriptomics between zebrafish, surface fish, and cavefish, we identified the fatty acid transporter slc27a2a/fatp2 to be correlated with the development of fatty liver. Pharmacological inhibition of slc27a2a in zebrafish rescues steatosis and atrophy of the liver upon starvation. Further, down-regulation of FATP2 in drosophila larvae inhibits the development of starvation-induced steatosis, suggesting the evolutionary conserved importance of the gene in regulating fatty liver upon nutrition deprivation. Overall, our study identifies a conserved, druggable target to protect the liver from atrophy during starvation.
2024-01-11 | GSE252997 | GEO
Project description:Peroxisome proliferator-activated receptor alpha (PPARα) is a key regulator of hepatic fat oxidation that serves as an energy source during starvation. Vanin-1 has been described as a putative PPARα target gene in liver, but its function in hepatic lipid metabolism is unknown. We investigated the regulation of vanin-1, and total vanin activity, by PPARα in mice and humans. Furthermore, the function of vanin-1 in the development of hepatic steatosis in response to starvation was examined in Vnn1 deficient mice, and in rats treated with an inhibitor of vanin activity. Liver microarray analyses reveals that Vnn1 is the most prominently regulated gene after modulation of PPARα activity. In addition, activation of mouse PPARα regulates hepatic- and plasma vanin activity. In humans, consistent with regulation by PPARα, plasma vanin activity increases in all subjects after prolonged fasting, as well as after treatment with the PPARα agonist fenofibrate. In mice, absence of vanin-1 exacerbates the fasting-induced increase in hepatic triglyceride levels. Similarly, inhibition of vanin activity in rats induces accumulation of hepatic triglycerides upon fasting. Microarray analysis reveal that the absence of vanin-1 associates with gene sets involved in liver steatosis, and reduces pathways involved in oxidative stress and inflammation. We show that hepatic vanin-1 is under extremely sensitive regulation by PPARα and that plasma vanin activity could serve as a readout of changes in PPARα activity in human subjects. In addition, our data propose a role for vanin-1 in regulation of hepatic TG levels during fasting. Livers of wild type and vanin-1 knockout mice that were fed or fasted for 24h were subjected to gene expression analysis
2014-04-24 | E-GEOD-51712 | biostudies-arrayexpress
Project description:Mice lacking TSKU exhibited elevated core body temperature and were unable to adequately suppress energy expenditure during starvation, leading to greater body weight loss. Tsku null mice were strongly resistant to diet-induced obesity and its associated metabolic disorders, including insulin resistance and hepatic steatosis. This metabolic phenotype was associated with sympathetic activation and enhanced brown fat thermogenesis. Here we used microarrays to uncover the metabolic pathways relevant to the phenotype induced by Tsku deficiency.
2019-01-01 | GSE114361 | GEO
Project description:To unveil HMGB1 DNA occupancy in livers of mice after a metabolic stress either induced by a 12-week high fat diet consumption or a fasting (6hours)-refeeding (8hours) challenge. Challenges known to generate a robust activation of hepatic lipogenesis and liver steatosis.
2022-03-31 | E-MTAB-11543 | biostudies-arrayexpress
Project description:Liver Macrophages exacerbate oxidative stress induced by hepatic steatosis in obesity by blocking the endogenous anti-oxidant response.
2019-06-21 | GSE132795 | GEO
Project description:Peroxisome proliferator-activated receptor alpha (PPARα) is a key regulator of hepatic fat oxidation that serves as an energy source during starvation. Vanin-1 has been described as a putative PPARα target gene in liver, but its function in hepatic lipid metabolism is unknown. We investigated the regulation of vanin-1, and total vanin activity, by PPARα in mice and humans. Furthermore, the function of vanin-1 in the development of hepatic steatosis in response to starvation was examined in Vnn1 deficient mice, and in rats treated with an inhibitor of vanin activity. Liver microarray analyses reveals that Vnn1 is the most prominently regulated gene after modulation of PPARα activity. In addition, activation of mouse PPARα regulates hepatic- and plasma vanin activity. In humans, consistent with regulation by PPARα, plasma vanin activity increases in all subjects after prolonged fasting, as well as after treatment with the PPARα agonist fenofibrate. In mice, absence of vanin-1 exacerbates the fasting-induced increase in hepatic triglyceride levels. Similarly, inhibition of vanin activity in rats induces accumulation of hepatic triglycerides upon fasting. Microarray analysis reveal that the absence of vanin-1 associates with gene sets involved in liver steatosis, and reduces pathways involved in oxidative stress and inflammation. We show that hepatic vanin-1 is under extremely sensitive regulation by PPARα and that plasma vanin activity could serve as a readout of changes in PPARα activity in human subjects. In addition, our data propose a role for vanin-1 in regulation of hepatic TG levels during fasting.
2014-04-24 | GSE51712 | GEO
Project description:Starvation is a severe form of malnutrition that occurs when an individual's intake of food is inadequate to meet their body's energy requirements. Prolonged starvation can cause permanent organ damage, stunted growth in children, and death if left untreated. It is estimated that approximately 45% of deaths among children under the age of 5 years are linked to undernutrition. Notably, the liver’s health is compromised during starvation. More than 60 years ago, it was recognized that chronic severe malnutrition in children, such as kwashiorkor, leads to fatty liver. Subsequently, starvation has been shown to induce accumulation of liver fat (steatosis) in drosophila, zebrafish, and humans. To uncover potential strategies for protecting the liver, we turned to adaptation strategies present in a genetically tractable and naturally occurring model of starvation resistance - the Astyanax mexicanus model system. Cave populations of this species have adapted to survive in conditions of extreme starvation, while the surface populations of the same species display relatively normal vertebrate physiology. We took advantage of this unique system to study the response of the liver to starvation and identified reduced expression of the fatty acid uptake gene slc27a2a/fatp2 allowing cavefish to prevent liver damage under starvation. Targeting this pathway in both fish and flies mitigates starvation-induced hepatic steatosis and protects the liver from lipotoxicity in zebrafish. This demonstrates that the identified pathway is evolutionary conserved for over 400 million years, highlighting its potential as a druggable target.
2024-01-11 | GSE244648 | GEO
Project description:Metabolic dysfunction-associated steatotic liver disease (MASLD) affects one third of the global population. Understanding metabolic pathways involved can provide insights into disease progression and treatment. Untargeted metabolomics of livers from mice with early-stage steatosis uncovered decreased methylated metabolites, suggesting altered one-carbon metabolism. The levels of glycine, a central component of one-carbon metabolism, were lower in mice with hepatic steatosis, consistent with clinical evidence. Stable-isotope tracing demonstrated that increased serine synthesis from glycine via reverse serine hydroxymethyltransferase (SHMT) is the underlying cause for decreased glycine in steatotic livers. Consequently, limited glycine availability in steatotic livers impaired glutathione synthesis under acetaminophen-induced oxidative stress, enhancing acute hepatotoxicity. Glycine supplementation or hepatocyte-specific
ablation of the mitochondrial SHMT2 isoform in mice with hepatic steatosis mitigated
acetaminophen-induced hepatotoxicity by supporting de novo glutathione synthesis. Thus, early metabolic changes in MASLD that limit glycine availability sensitize mice to xenobiotics even at the reversible stage of this disease.
2023-12-12 | MSV000093653 | MassIVE
Project description:The study was designed to determine the effect of inhibition of ileal bile acid uptake on hepatic gene expression in high fat diet induced hepatic steatosis in mice
2016-09-22 | GSE84994 | GEO
Project description:Starvation resistant cavefish reveal conserved mechanisms of starvation-induced hepatic lipotoxicity
| PRJNA1023959 | ENA