Mus musculus breed:C57BL/6 N
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ABSTRACT:
PROVIDER: PRJNA1159526 | ENA |
REPOSITORIES: ENA
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Project description:Nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1), an NAD+ synthetase in Preiss-Handler and salvage pathways, governs nuclear NAD+ homeostasis. This study investigated the role of NMNAT1 on alcohol-associated liver disease (ALD). Decreased NMNAT1 expression and activity were observed in the liver of alcohol-associated hepatitis patients and either liver or primary hepatocytes from ALD mice. F-box and WD repeat domain containing 7 (FBXW7)-regulated interferon regulatory factor 1 (IRF1) ubiquitination degradation contributed to alcohol-inhibited NMNAT1 transcriptional level. Hepatic NMNAT1 knockout aggravated alcohol-induced hepatic NAD+ decline and further hepatic steatosis and liver injury. Metabolomics and transcriptomics interaction revealed that cysteine sulfinic acid decarboxylase (CSAD)-regulated taurine pathway was involved in NMNAT1-disrupted hepatic lipid metabolism in ALD. Hepatic CSAD overexpression or taurine supply attenuated hepatic NMNAT1 knockout-aggravated ALD, respectively. Hepatic NMNAT1 loss inhibited NMN-protected ALD. Replenishing hepatic NMNAT1 reversed liver lipid accumulation in ALD mice. These findings identified NMNAT1 as a promising therapeutic target for ALD.
2025-05-25 | GSE297696 | GEO
Project description:The tumor suppressor p53 is critical for tumor suppression and other biological events. Yet, the regulatory role of p53 in alcohol-induced fatty liver remains unclear. Here, we show a role for p53 in regulating the ethanol metabolism via acetaldehyde dehydrogenase 2 (ALDH2), a key enzyme responsible for oxidization of alcohol. Through repressing ethanol oxidization, p53 suppresses intracellular levels of acetyl-CoA and histone acetylation, leading to the inhibition of the stearoyl-CoA desaturase-1 (SCD1) gene expression. Mechanistically, p53 directly binds to ALDH2 and prevents the formation of its active tetramer, and indirectly limits the production of pyruvate that promotes the activity of ALDH2. Notably, p53 deficient mice exhibit increased lipid accumulation, which can be reversed by ALDH2 depletion. Moreover, hepatic specific knockdown of SCD1 diminishes ethanol-induced fatty liver caused by p53 loss. By contrast, overexpression of SCD1 in liver promotes ethanol-induced fatty liver development in wildtype mice, while has mild effect on p53-/- or ALDH2-/- mice. Overall, our findings reveal a previously unrecognized function of p53 in alcohol-induced fatty liver, and uncover pyruvate as a natural regulator of ALDH2.
2023-02-08 | GSE222743 | GEO
Project description:Alcohol induced fatty liver cause a dangerous health problem and is the major cause of morbidity and mortality worldwide. Garlic (Allium sativum) is documented to possess anti-fatty liver properties. However the exact molecular mechanisms are unknown. The main aim of this experiment is to elucidate the underlying pathways through which garlic ameliorates alcohol induced fatty liver. Dially disulfide and garlic oil were the garlic compounds used in this study. Leiber DeCarli ethanol liquid diet was to induce fatty liver in C57BL/6 mice model. Also the expression impaired by alcohol induced fatty liver is another aim of this study.
2012-10-01 | GSE40334 | GEO
Project description:To investigate the function of read-through circRNAs in liver, we obtained human NASH liver tissues and normal liver tissues patients without NAFLD undergoing surgery for hepatic hemangioma.Patients with positive hepatitis B surface antigen or anti-hepatitis C virus (HCV) antibody with detectable HCV RNA, excessive alcohol consumption (20 g/day in men or 10 g/day in women), secondary fatty liver (e.g., use of systemic steroids or tamoxifen), or malignancies before baseline were excluded. We then performed exome capture mRNA sequencing using livers from three NASH patients and three patients with hepatic hemangioma.
2022-09-08 | GSE212741 | GEO
Project description:Alcoholic liver diseases (ALDs) encompass a broad spectrum of clinical features of alcoholic fatty liver, alcoholic steatohepatitis and cirrhosis, and increased risk of hepatocellular carcinoma. While the toxic effects of alcohol likely result from complex interactions between genes and the environment, the molecular mechanisms of alcohol-induced liver damage remains undefined. Thus, a better understanding of the mechanisms regulating hepatic cell injury may lead to more effective therapeutic approaches for ALD. Here we compared the miRNA expression profile from tissues from control mice and mice receiving intragastric ethanol feeding. Four microarray hybridization studies were performed on three different pairs of liver-derived RNA from intragastric ethanol feeding and normal mice. The miRNAs differentially overexpressed in livers from ethanol fed mice.
2014-10-07 | E-MTAB-2311 | biostudies-arrayexpress
Project description:Alcohol induced fatty liver cause a dangerous health problem and is the major cause of morbidity and mortality worldwide. Garlic (Allium sativum) is documented to possess anti-fatty liver properties. However the exact molecular mechanisms are unknown. The main aim of this experiment is to elucidate the underlying pathways through which garlic ameliorates alcohol induced fatty liver. Dially disulfide and garlic oil were the garlic compounds used in this study. Leiber DeCarli ethanol liquid diet was to induce fatty liver in C57BL/6 mice model. Also the expression impaired by alcohol induced fatty liver is another aim of this study. Leiber-Decarli ethanol diet was used to induce fatty liver in male C57BL/6 mice (n=12). For control, Lieber-DeCarli liquid control diet was fed to mice (n=4). The control mice were pair-fed to the ethanol mice. After adaptation, the ethanol fed mice were divided into three groups viz. alcohol (n=4), dially disulfide [DADS] (n=4) and garlic oil [GO] (n=4). The study started with the administration of DADS (15 mg/kg bw) or GO (50 mg/kg bw) mixed in 0.1 ml olive oil through gavage. For the control and alcohol groups, same amount of olive oil (0.1 ml) was gavaged. The mice were gavaged daily for 4 weeks. The mice were euthanized by CO2 and blood was collected by cardiac puncture. Liver, kidney, spleen, lungs and hearts were collected and their weights recorded. A portion of liver was snap frozen in liquid nitrogen (200 mg) for RNA extraction.
2012-10-01 | E-GEOD-40334 | biostudies-arrayexpress
Project description:Obesity is tightly associated with an increased risk of nonalcoholic fatty liver disease (NAFLD). However, the molecular mechanisms of obesity-induced fatty liver remain largely unknown.In order to identify genes that are potentially involved in dysfunctional hepatic lipid homeostasis in obesity, we performed a clustering analysis of Affymetrix arrays,which revealed that a number of mRNAs were dys-regulated in the livers of mice fed a high-fat diet (HFD), compared with mice fed a normal chow diet (ND). To identify genes that are potentially involved in dysfunctional hepatic lipid homeostasis in obesity, male C57BL/6 mice aged 8 weeks were fed a normal diet (ND) or high-fat-diet (HFD) containing 60 Kcal% of fat for 12 weeks. Then mice were sacrificed and total RNAs were isoloated from hepatic tissues. Affymetrix array hybridisation and scanning were performed using Mouse Genome 430 2.0 chips.Total RNA samples obtained from six mice per group (ND and HFD) and pooled by each of the two were used for microarray analysis.
2014-05-09 | E-GEOD-57425 | biostudies-arrayexpress
Project description:The aim of the study is to investigate the role and mechanisms of tuberous sclerosis complex 1 (TSC1) and mechanistic target of rapamycin complex 1 (mTORC1) in alcohol associated liver disease Hepatic RNA profiles of WT and hepatic TSC1 KO mice fed with alcohol or control diet using Gao binge alcohol model.
2023-04-25 | GSE230175 | GEO
Project description:Obesity is tightly associated with an increased risk of nonalcoholic fatty liver disease (NAFLD). However, the molecular mechanisms of obesity-induced fatty liver remain largely unknown.In order to identify genes that are potentially involved in dysfunctional hepatic lipid homeostasis in obesity, we performed a clustering analysis of Affymetrix arrays,which revealed that a number of mRNAs were dys-regulated in the livers of mice fed a high-fat diet (HFD), compared with mice fed a normal chow diet (ND).
2014-05-09 | GSE57425 | GEO
Project description:Introduction: Diet-induced obesity is associated with hepatic lipid accumulation, increased circulating levels of endotoxin, and chronic low grade inflammation. Hepatic lipid accumulation and resulting non-alcoholic fatty liver disease (NAFLD) can exacerbate systemic inflammation further contributing to neurodegenerative effects. Maple Syrup Extract (MSX), could be a potential source of beneficial phytonutrients capable of mitigating these adverse inflammatory processes from occurring. Methods: A pilot scale diet-induced obesity study with male C57BL/6 mice fed either a standard diet (10% kcal from fat) or a high fat diet (45% kcal from fat) with or without MSX at a dose of 0.5% w/w incorporated into feed for 12 weeks. Livers and whole hippocampi were excised for multiplex gene expression analysis of inflammatory, fatty liver, and neurodegenerative disease associated genes. Livers were scored for lipid accumulation and lipid moieties were quantified. Results: In hepatic tissue, MSX protected against lipid accumulation and inflammatory progression. MSX supplementation significantly reduced lipid accumulation scores as well as gene expression of lipid uptake, storage, and inflammatory associated genes. In the hippocampus, MSX supplementation in HFD feed significantly reduced the gene expression of pro-inflammatory, death receptor ligands, anti-oxidant response enzymes, macrophage receptors, and leptin receptor. Conclusions: In the liver, MSX prevents gross hepatic lipid accumulation and suppresses both pro-inflammatory and lipid storage associated genes. In the hippocampus, MSX may act on pro-inflammatory gene expression but TNF mediated death receptor pathways in addition to modulating leptin receptor signaling.
2019-05-21 | GSE131495 | GEO