Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA258077 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Abnormalities in hepatic lipid metabolism are believed to play a critical role in the etiology of nonalcoholic steatohepatitis (NASH). Monoacylglycerol acyltransferase (MGAT) enzymes convert monoacylglycerol to diacylglycerol, which is the penultimate step in one pathway for triacylglycerol (TAG) synthesis. Hepatic expression of Mogat1, which encodes an MGAT enzyme, is increased in the livers of mice with hepatic steatosis and knocking down Mogat1 improves insulin sensitivity, but whether increased MGAT activity plays a role in the etiology of NASH is unclear. To examine the effects of knocking down Mogat1 in the liver on the development of NASH, C57BL/6 mice were placed on a diet containing high levels of trans fatty acids, fructose, and cholesterol (HTF-C diet) or a low fat control diet for 4 weeks. Mice were then injected with antisense oligonucleotides (ASO) to knockdown Mogat1 or a scrambled ASO control for 12 weeks while remaining on diet. HTF-C diet caused glucose intolerance, hepatic steatosis, and induced hepatic gene expression markers of inflammation, macrophage infiltration, and stellate cell activation. Mogat1 ASO treatment, which suppressed Mogat1 expression in liver, attenuated weight gain, improved glucose tolerance, and decreased hepatic TAG content compared to control ASO-treated mice on HTF-C chow. However, Mogat1 ASO treatment did not reduce hepatic DAG, cholesterol, or free fatty acid content, improve histologic measures of liver injury, or reduce expression of markers of stellate cell activation, liver inflammation, and injury. In conclusion, inhibition of hepatic Mogat1 in HTF-C diet-fed mice improves glucose tolerance and hepatic TAG accumulation without attenuating liver inflammation and injury. Total RNA obtained from liver of 4 control vs. 4 Mogat1 ASO treated higf-fat diet (HFD) fed mice.
2014-11-05 | E-GEOD-60349 | biostudies-arrayexpress
Project description:Abnormalities in hepatic lipid metabolism are believed to play a critical role in the etiology of nonalcoholic steatohepatitis (NASH). Monoacylglycerol acyltransferase (MGAT) enzymes convert monoacylglycerol to diacylglycerol, which is the penultimate step in one pathway for triacylglycerol (TAG) synthesis. Hepatic expression of Mogat1, which encodes an MGAT enzyme, is increased in the livers of mice with hepatic steatosis and knocking down Mogat1 improves insulin sensitivity, but whether increased MGAT activity plays a role in the etiology of NASH is unclear. To examine the effects of knocking down Mogat1 in the liver on the development of NASH, C57BL/6 mice were placed on a diet containing high levels of trans fatty acids, fructose, and cholesterol (HTF-C diet) or a low fat control diet for 4 weeks. Mice were then injected with antisense oligonucleotides (ASO) to knockdown Mogat1 or a scrambled ASO control for 12 weeks while remaining on diet. HTF-C diet caused glucose intolerance, hepatic steatosis, and induced hepatic gene expression markers of inflammation, macrophage infiltration, and stellate cell activation. Mogat1 ASO treatment, which suppressed Mogat1 expression in liver, attenuated weight gain, improved glucose tolerance, and decreased hepatic TAG content compared to control ASO-treated mice on HTF-C chow. However, Mogat1 ASO treatment did not reduce hepatic DAG, cholesterol, or free fatty acid content, improve histologic measures of liver injury, or reduce expression of markers of stellate cell activation, liver inflammation, and injury. In conclusion, inhibition of hepatic Mogat1 in HTF-C diet-fed mice improves glucose tolerance and hepatic TAG accumulation without attenuating liver inflammation and injury.
2014-11-05 | GSE60349 | GEO
Project description:Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder with high morbidity and mortality. The current study aims to explore the role of Cullin-associated and neddylation-dissociated protein 1 (CAND1) in the development of NAFLD and the underlying mechanisms. CAND1 is reduced in the liver of NAFLD male patients and high fat diet (HFD)-fed male mice. CAND1 alleviates palmitate (PA) induced lipid accumulation in vitro. Hepatocyte-specific knockout of CAND1 exacerbates HFD-induced liver injury in HFD-fed male mice, while hepatocyte-specific knockin of CAND1 ameliorates these pathological changes. Mechanistically, deficiency of CAND1 enhances the assembly of Cullin1, F-box only protein 42 (FBXO42) and acetyl-CoA acyltransferase 2 (ACAA2) complexes, and thus promotes the ubiquitinated degradation of ACAA2. ACAA2 overexpression abolishes the exacerbated effects of CAND1 deficiency on NAFLD. Additionally, androgen receptor binds to the -187 to -2000 promoter region of CAND1. Collectively, CAND1 mitigates NAFLD by inhibiting Cullin1/FBXO42 mediated ACAA2 degradation
2023-10-24 | PXD043719 | Pride
Project description:Inhibiting hepatic LPCAT3 ameliorates alcoholic liver injury through regulating NAMPT and PTLP signaling
| PRJNA1141368 | ENA
Project description:Cannabinoid 1 receptor (CB1R) expression is upregulated in hepatocytes during viral hepatitis, cirrhosis, and both alcoholic and non-alcoholic fatty liver disease (FLD), whereas its expression is muted under usual physiological conditions. Inhibiting CB1R has been shown to be beneficial in preserving hepatic function in FLD but it is unclear if inhibiting CB1R during an inflammatory response to an acute hepatic injury, such as toxin - induced injury, would also be beneficial. We tested if nullification of hepatocyte-specific CB1R (hCNR1-/-) in mice protects against concanavalin A (Con A) - induced liver injury. We looked for evidence of liver damage and markers of inflammation in response to Con A by measuring liver enzyme levels and proinflammatory cytokines (e.g., TNF-α, IL-1β, IL-6, IL-17) in serum collected from hCNR1-/- and control mice. We observed a shift to the right in the dose-response curve for liver injury and inflammation in hCNR1-/- mice. We also found less inflammatory cell infiltration and focal necrosis in livers of hCNR1-/- mice compared to controls, resulting from downregulated apoptotic markers. This anti-apoptotic mechanism results from increased activation of nuclear factor kappa B (NF-κB), especially membrane-bound TNF-α, via downregulated TNF-α receptor 2 (TNFR2) transcription levels. We also found that CB1R in hepatocytes regulated liver inflammation - related gene transcription. Collectively, these findings provide insight into involvement of CB1R in the pathogenesis of acute liver injury.
2020-12-22 | GSE148309 | GEO
Project description:Here, we found that microRNA-223 (miR-223) was highly elevated in hepatocytes after high fat diet (HFD) feeding in mice and in human nonalcoholic steatohepatitis (NASH) samples. Genetic deletion of the miR-223 induced a full spectrum of nonalcoholic fatty liver disease (NAFLD) in mice after long-term (up to one year) HFD feeding including NASH-related steatosis, inflammation, fibrosis and HCC. To better explore the mechanisms underlying the abnormalities observed in HFD-fed miR-223KO mice, we examined hepatic gene expression in 3-month-HFD-fed WT and miR-223KO mice by microarray analysis. Finally, we revealed that miR-223 plays a key role in controlling steatosis-to-NASH progression by inhibiting hepatic Cxcl10 and Taz expression.
2019-03-30 | GSE129080 | GEO
Project description:In this study, we identified Receptor interacting protein kinase 1 (RIPK1) in hepatocytes as a critical regulator in preserving hepatic homeostasis during metabolic challenges, such as short-term fasting or high-fat dieting. Our results demonstrated that hepatocyte-specific deficiency of RIPK1 sensitized the liver to short-term fasting-induced liver injury and hepatocyte apoptosis in both male and female mice. Despite being a common physiological stressor that typically does not induce liver inflammation, short-term fasting triggered hepatic inflammation and compensatory proliferation in hepatocyte-specific RIPK1-deficient (Ripk1Δhep) mice. Transcriptomic analysis revealed that short-term fasting oriented the hepatic microenvironment into an inflammatory state in Ripk1Δhep mice, with upregulated expression of inflammation and immune cell recruitment-associated genes. Single-cell RNA sequencing further confirmed the altered cellular composition in the liver of Ripk1Δhep mice during fasting, highlighting the increased recruitment of macrophages to the liver.
2025-01-11 | GSE286073 | GEO
Project description:In this study, we identified Receptor interacting protein kinase 1 (RIPK1) in hepatocytes as a critical regulator in preserving hepatic homeostasis during metabolic challenges, such as short-term fasting or high-fat dieting. Our results demonstrated that hepatocyte-specific deficiency of RIPK1 sensitized the liver to short-term fasting-induced liver injury and hepatocyte apoptosis in both male and female mice. Despite being a common physiological stressor that typically does not induce liver inflammation, short-term fasting triggered hepatic inflammation and compensatory proliferation in hepatocyte-specific RIPK1-deficient (Ripk1Δhep) mice. Transcriptomic analysis revealed that short-term fasting oriented the hepatic microenvironment into an inflammatory state in Ripk1Δhep mice, with upregulated expression of inflammation and immune cell recruitment-associated genes. Single-cell RNA sequencing further confirmed the altered cellular composition in the liver of Ripk1Δhep mice during fasting, highlighting the increased recruitment of macrophages to the liver.
2025-01-11 | GSE286072 | GEO
Project description:Resveratrol ameliorates Imiquimod-induced psoriasis-like skin inflammation in mice
| PRJNA268687 | ENA
Project description:Scavenger receptor A ameliorates acetaminophen induced hepatic inflammation
| PRJNA915955 | ENA