Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA263597 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Alterations in endoplasmic reticulum (ER) homeostasis have been implicated in the pathophysiology of obesity and type-2 diabetes (T2D). Acute ER stress induction in the hypothalamus produces glucose metabolism perturbations. However, the neurobiological basis linking hypothalamic ER stress with abnormal glucose metabolism remains unknown. Here we report that genetic and induced models of hypothalamic ER stress are associated with alterations in systemic glucose homeostasis due to increased gluconeogenesis (GNG) independent of body weight changes. Defective alpha melanocyte-stimulating hormone (a-MSH) production underlies this metabolic phenotype, as pharmacological strategies aimed at rescuing hypothalamic a-MSH content reversed this phenotype at metabolic and molecular level. Collectively, our results posit defective a-MSH processing as a fundamental mediator of enhanced GNG in the context of hypothalamic ER stress, and establish a-MSH deficiency in proopiomelanocortin (POMC) neurons as a potential contributor to the pathophysiology of T2D. Total RNA was extracted from whole-liver of 6-week old control (3 biological replicates) and POMCMfn2KO mice (5 biological replicates)
2015-06-18 | E-GEOD-62263 | biostudies-arrayexpress
Project description:Alterations in endoplasmic reticulum (ER) homeostasis have been implicated in the pathophysiology of obesity and type-2 diabetes (T2D). Acute ER stress induction in the hypothalamus produces glucose metabolism perturbations. However, the neurobiological basis linking hypothalamic ER stress with abnormal glucose metabolism remains unknown. Here we report that genetic and induced models of hypothalamic ER stress are associated with alterations in systemic glucose homeostasis due to increased gluconeogenesis (GNG) independent of body weight changes. Defective alpha melanocyte-stimulating hormone (a-MSH) production underlies this metabolic phenotype, as pharmacological strategies aimed at rescuing hypothalamic a-MSH content reversed this phenotype at metabolic and molecular level. Collectively, our results posit defective a-MSH processing as a fundamental mediator of enhanced GNG in the context of hypothalamic ER stress, and establish a-MSH deficiency in proopiomelanocortin (POMC) neurons as a potential contributor to the pathophysiology of T2D.
2015-06-18 | GSE62263 | GEO
Project description:O-GlcNAcylation is a reversible post-translational modification controlled by the activity of two enzymes, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). In the liver, O-GlcNAcylation has emerged as an important regulatory mechanism underlying normal liver physiology and metabolic disease.To address whether OGT acts as a critical hepatic nutritional node, mice with a constitutive hepatocyte-specific deletion of OGT (OGTLKO) were generated.Analyses of 4-week-old OGTLKO mice revealed significant oxidative and endoplasmic reticulum stress, and DNA damage, together with inflammation and fibrosis, in the liver. Susceptibility to oxidative and endoplasmic reticulum stress- induced apoptosis was also elevated in OGTLKO hepatocytes. Although OGT expression was partially recovered in the liver of 8- week-old OGTLKO mice, hepatic injury and fibrosis were not rescued but rather worsened with time. Interestingly, weaning of OGTLKO mice on a ketogenic diet (low carbohydrate, high fat) fully prevented the hepatic alterations induced by OGT deletion, indicating that reduced carbohydrate intake protects an OGT-deficient liver. These findings pinpoint OGT as a key mediator of hepatocyte homeostasis and survival upon carbohydrate intake and validate OGTLKO mice as a valuable model for assessing therapeutical approaches of advanced liver fibrosis.
2024-03-12 | GSE261136 | GEO
Project description:We examined the effect of oral TUDCA treatment on hepatic steatosis and associated changes in hepatic gene expression in ob/ob mice. We administered TUDCA to ob/ob mice at a dose of 500 mg/kg twice a day by gastric gavage for 3 weeks. Body weight, glucose homeostasis, endoplasmic reticulum (ER) stress, and hepatic gene expression were examined in comparison with control ob/ob mice and normal littermate C57BL/6J mice.
2010-12-31 | E-GEOD-22608 | biostudies-arrayexpress
Project description:Reduced insulin production relieves endoplasmic reticulum stress and induces beta-cell proliferation
| PRJNA299027 | ENA
Project description:Vertical sleeve gastrectomy reduces blood pressure and hypothalamic endoplasmic reticulum stress in mice
| PRJEB19390 | ENA
Project description:We report the RNA-sequencing analysis of hepatic RNA isolated from CD-1 mice following gestational exposure to 500ppb CdCl2. We show that gestational Cd exposure alters the hepatic gene expression of female, but not male offspring in numerous pathways related to oxidative stress and mitochondrial dysfunction leading to endoplasmic reticulum stress that ultimately drives metabolic disruption of insulin signaling.
2020-12-09 | GSE150679 | GEO
Project description:The hepatic unfolded protein response (UPR) is an adaptive cellular response to endoplasmic reticulum stress that is important in the pathogenesis of many liver diseases. In this study, we utilized liver biopsies from patients after liver transplantation as a disease model to determine the transcriptional profile and hepatic UPR gene expression that is associated with liver injury and cholestasis.
2022-08-17 | GSE203453 | GEO
Project description:The hepatitis E virus (HEV), a non enveloped RNA virus, causes viral hepatitis. The viral open reading frame 2 (ORF2) protein represents the capsid protein of HEV which is known to cause endoplasmic reticulum stress in ORF2 expressing cells. The initiation of endoplasmic reticulum stress induced apoptosis mainly involves the transcriptional activation of pro-apoptotic gene CHOP which will further trigger the major apoptotic pathways. However, the activation of CHOP by ORF2 protein in this study does not induce apoptotic markers such as Bax translocation to mitochondria. We have used the Affymetrix microarray platform to screen the pro-apoptotic effects induced by the expression of ORF2 protein in human hepatic cell lines (Huh7). The Huh7 cells were transduced either with recombinant adenovirus encoding the HEV ORF2 (Ad-ORF2) or an adenovirus encoding the green fluorescent protein (Ad-GFP). The array results consistently showed an ORF2 specific induction of mRNA corresponding to the chaperones Hsp72, Hsp70B’ and co-chaperone Hsp40. These studies provide further mechanisms of the ER stress mediated pro apoptotic effects caused by the ORF2 protein and its potential role for the activation of anti-apoptotic activity of the host cell. We used microarray to screen the host genes were regulated by the expression of the hepatitis E virus capsid protein. Huh7 cells transduced with Ad-GFP (control) or with Ad-HEV ORF2.
2012-12-01 | E-GEOD-29061 | biostudies-arrayexpress
Project description:Endoplasmic reticulum oxidoreductase 1 alpha (ERO1α) is an endoplasmic reticulum stress–related gene, which improves cell perseverance against challenges of high levels of protein misfolding during endoplasmic reticulum stress by retaining good activity of oxidative protein folding. Numerous studies have shown abnormal expression of ERo1α in various diseases, but its downstream target are not fully understood. Our work will help in the elucidation of the downstream molecular mechanism of ERO1α.
2024-04-17 | GSE246899 | GEO