Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Pathway Preferential Estrogens prevent hepatosteatosis due to ovariectomy and high-fat diets

ABSTRACT: Pathway preferential estrogen 1 (PaPE-1) is a novel estrogen receptor ligand that has been shown to favorably affect metabolic tissues without adverse effects on reproductive tissues. In this study, we have examined the effects of PaPE-1 on metabolic health, in particular, examin-ing its effects on the liver transcriptome and on plasma metabolites in two different mouse mod-els: diet-induced obesity (DIO) and leptin-deficient (ob/ob) mice. PaPE-1 significantly decreased liver weight and lipid accumulation in both DIO and ob/ob models and lowered the expression of genes associated with fatty acid metabolism and collagen deposition. Overall, our findings support a beneficial metabolic role for PaPE-1 and suggest that PaPE-1 may protect postmenopausal women from fatty liver disease without increasing reproductive cancer risk.

ORGANISM(S): Mus musculus

PROVIDER: GSE181780 | GEO | 2024/08/10

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Leptin Signalling in the Ovary of Diet-Induced Obese Mice Regulates Activation of Nod-Like Receptor Protein 3 Inflammasome

Project description:Obesity leads to ovarian dysfunction and the establishment of local leptin resistance. The aim of our study was to characterise levels of Nod-Like Receptor Protein 3 (NLRP3) inflammasome activation during obesity progression in the mouse ovaries and liver and test the putative role of leptin on its regulation. C57BL/6J mice were treated with equine chorionic gonadotropin (eCG) or human chorionic gonadotropin (hCG) for oestrous cycle synchronisation and ovaries collection. In diet-induced obesity (DIO) model, mice were fed chow diet (CD) or high fat diet (HFD) for 4 or 16 weeks (wk), whereas in hyperleptinemic model (LEPT), mice were injected with leptin for 16 days (16L) or saline (16C) and in the genetic obese leptin-deficient ob/ob (+/? and -/-) animals were fed CD for 4wk. Either ovaries and liver were collected, as well as cumulus cells (CCs) after superovulation from DIO and LEPT. In DIO protocol, protein expression of NLRP3 inflammasome components was increased in 4wk HFD, but decreased in 16wk HFD. Moreover LEPT and ob/ob models revealed NLRP3 and IL-1 upregulation in 16L and downregulation in ob/ob. Transcriptome analysis of CC showed common genes between LEPT and 4wk HFD modulating NLRP3 inflammasome. Moreover analysis in the liver showed upregulation of NLRP3 protein only after 16wk HFD, but also the downregulation of NLRP3 protein in ob/ob-/-. We showed the link between leptin signalling and NLRP3 inflammasome activation in the ovary throughout obesity progression in mice, elucidating the molecular mechanisms underpinning ovarian failure in maternal obesity.

2021-11-01 | GSE180300 | GEO

Differential Expression of MicroRNAs in Mouse Liver under Aberrant Energy Metabolic Status

Project description:Despite years of effort, exact pathogenesis of non-alcoholic fatty liver disease (NAFLD) remains obscure. To gain an insight into the regulatory roles of microRNAs (miRNAs) in aberrant energy metabolic status and pathogenesis of NAFLD, we analyzed the expression of miRNAs in livers of ob/ob mice, streptozotocin (STZ)-induced type 1 diabetic mice and normal C57BL/6 mice by miRNA microarray. Compared to normal C57BL/6 mice, ob/ob mice showed up-regulation of 8 miRNAs and down-regulation of 4 miRNAs in fatty livers. Up-regulation of miR-34a and down-regulation of miR-122 was found in livers of STZ-induced diabetic mice. These results demonstrate that distinct miRNAs are strongly dysregulated in NAFLD and hyperglycemia. Comparison between miRNA expressions in livers of ob/ob mice and STZ-administered mice further revealed up-regulation of 4 miRNAs and down-regulation of 2 miRNAs in livers of ob/ob mice, indicating that these miRNAs may represent a molecular signature of NAFLD. A distinctive miRNA expression pattern was identified in ob/ob mouse liver and hierarchical clustering of this pattern could clearly discriminate ob/ob mice from either normal C57BL/6 mice or STZ-administered mice. These findings suggest an important role of miRNAs in hepatic energy metabolism and implicate the participation of miRNAs in the pathophysiological processes of NAFLD. Keywords: disease state analysis In the present study, we analyzed the expression of miRNAs in livers of 10 ob/ob mice, 8 streptozotocin (STZ)-induced type 1 diabetic mice and 8 normal control C57BL/6 mice by miRNA microarray.

2010-05-18 | E-GEOD-13840 | biostudies-arrayexpress

Gene expression in diet-induced obesity resistent (DIO non-responder) and diet-induced obesity susceptible (DIO responder) C57BL/6J mouse strain

Project description:Inbred C57BL/6J mice differ in their susceptibility to diet-induced obesity. Comparison of the liver transcriptomes leads to genes that are involved in the development as well as the maintenance of fatty liver during the onset of obesity upon high fat diet feeding. Genes being upregulated in DIO responder can be seen as drivers of fatty liver development, while genes upregulated in DIO non-responder are most likely involved in the protection against fatty liver diseases.

2018-10-30 | GSE74542 | GEO

Effect of ovariectomy and LCAT overexpression on gene expression of mouse liver cancer

Project description:To unravel the molecular mechanisms behind estrogen-mediated alleviation of liver cancer, we initially established a liver cancer model in ovariectomized mice. Through cross-species comparison of differentially expressed genes under estrogen dominance in human and murine liver cancers, we identified LCAT as a crucial downstream molecule mediating estrogen-induced gender disparities in liver cancer. Subsequent transcriptome sequencing of mouse liver tissues overexpressing the LCAT gene revealed that LCAT plays a pivotal role in inhibiting the cholesterol synthesis pathway, potentially serving as a key molecular mechanism through which it suppresses the occurrence and progression of liver cancer.

2024-02-19 | GSE255753 | GEO

Differential Expression of MicroRNAs in Mouse Liver under Aberrant Energy Metabolic Status

2009-12-04 | GSE13840 | GEO

PolyA-enriched RNA-Seq of livers from male and female C57Bl/6J mice fed a control or high-fat diet and treated with estrogen receptor agonists

Project description:Metabolic dysfunction-associated fatty liver disease is the most prevalent liver disease and affects a quarter of the global population. Estrogens are associated to safeguard the liver from metabolic diseases. We fed male and female mice a control or high-fat diet for 13 weeks. Only male mice developed fatty livers. We injected a subset of male mice fed a high-fat diet with four different estrogen receptor (ER) agonists for the last three weeks of the high-fat diet, activating the nuclear ERalpha and ERbeta. Livers were collected and flash-frozen before RNA isolation, DNAse treatment, library preparation and sequencing on an Illumina NextSeq 500 instrument.

2024-02-22 | E-MTAB-11833 | biostudies-arrayexpress

The Plant-derived Lipoxygenase Inhibitor Nordihydroguaiaretic Acid (NDGA) Attenuates Dyslipidemia and Hepatic Steatosis by Enhancing Fatty Acid Oxidation through Activation of PPAR-alpha

Project description:To test whether NDGA attenuate dyslipidemia and hepatic steatosis by enhancing fatty acid oxidation through activation of PPAR-α. Using wild type (WT, C57BL/6) fed with chow diet as control, WT mice were either fed with high-fat diet or high-fat diet with NDGA (2.5g/kg food); ob/ob mice were fed with either chow or chow with NDGA (2.5 g/kg food), and maintained on the respective diets for 16 weeks. The expression of lipid metabolism related genes in the liver of these mice were analyzed using Phalanx GPL6845 platform (Mouse OneArray V1). Together with other biochemical/physiological data, our results suggest that the beneficial actions of NDGA on dyslipidemia and hepatic steatosis in ob/ob mice are exerted primarily through enhanced fatty acid oxidation and energy utilization via the activation of PPAR- α receptor activity. To examine the changes in gene expression in liver of WT and ob/ob mice with different NDGA diet treatment, RNA isolated from 3 animals of each group were used for studies of gene expression profiles. Phalanx GPL6845 platform (Mouse OneArray V1) was used for the microarrays analysis.

2012-03-29 | E-GEOD-35075 | biostudies-arrayexpress

Integrated liver and plasma proteomics in obese mice reveals complex metabolic and immune regulation

Project description:Obesity leads to the development of non-alcoholic fatty liver disease (NAFLD) and associated alterations to the plasma proteome. To elucidate the underlying changes associated with obesity, we performed liquid chromatography-tandem mass spectrometry in the liver and plasma of obese leptin-deficient ob/ob mice. We quantified 7173 and 555 proteins in the liver and plasma, respectively. The abundance of proteins related to fatty acid metabolism were increased, alongside peroxisomal proliferation in ob/ob liver. Putatively secreted proteins and the secretory machinery were also dysregulated in the liver, which was mirrored by a substantial alteration of the plasma proteome. Greater than 50% of the plasma proteins were differentially regulated, including NAFLD biomarkers, lipoproteins, the 20S proteasome, and the complement and coagulation cascades of the immune system. Integration of the proteomes identified proteins that were concomitantly regulated in the liver and plasma in obesity, suggesting the systemic abundance of these plasma proteins are regulated by secretion from the liver. These analyses yield a comprehensive insight into obesity and provide an extensive resource for obesity research in a prevailing model organism.

2022-03-01 | PXD026821 | Pride

Mus musculus

Project description:Estrogen signaling and fatty liver disease

| PRJNA376559 | ENA

Development of Pathway Preferential Estrogens Affording Beneficial Metabolic and Vascular Actions without Reproductive Tissue Stimulation in Mice

Project description:There is great medical need for estrogens having favorable pharmacological profiles, supporting desirable activities for menopausal women such as metabolic and vascular protection but lacking stimulatory activities on the breast or uterus. Here, we report the development of structurally novel estrogens with favorable target tissue-selective estrogenic activity. Through a process of structural alteration of the hormone estradiol that preserves essential chemical and physical features of estradiol but greatly moderates its binding affinity for the estrogen receptors (ERs), we obtained Pathway Preferential Estrogens (PaPEs) capable of having interaction with ER that is sufficient to activate the extranuclear-initiated signaling pathway preferentially over the direct nuclear-initiated pathway. PaPE modulate a pattern of gene regulation and cellular and biological processes that result in essentially no stimulation of reproductive and mammary tissues and breast cancer cells, but have a favorable pattern of activity on metabolic tissues and the vasculature. The structural permutation process represents a novel approach to govern the balance in utilization of extranuclear vs. nuclear pathways of ER action to obtain tissue-selective/non-nuclear pathway-preferential estrogens, which should prove to be beneficial for postmenopausal hormone replacement. The approach may also have broad applicability for other members of the nuclear hormone receptor superfamily. 24 samples; inhibitor and time course experiments

2016-07-20 | E-GEOD-73663 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data