Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNA-sequencing of inguinal white adipose tissue (iWAT) from kynurenine 3-monooxygenase (Kmo) knockout mice and wild-type littermates on chow and high-fat diets.

ABSTRACT: To investigate if chronically elevated circulating kynurenic acid (KYNA) and reduced quinolinic acid (QUIN) levels affect whole-body energy metabolism, we used a knockout-first gene targeting strategy to eliminate Kmo gene expression in mice. We conducted a series of metabolic assessments on male and female mice fed either a chow or high-fat diet (HFD) and performed RNA-sequencing on the inguinal white adipose tissue (iWAT) from male Kmo-defficient mice and their wild-type littermate controls on chow and high-fat diets.

ORGANISM(S): Mus musculus

PROVIDER: GSE277692 | GEO | 2025/02/08

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

RNA-sequencing of inguinal white adipose tissue (iWAT) from kynurenine 3-monooxygenase (Kmo) knockout mice and wild-type littermates on chow and high-fat diets.

Project description:RNA-sequencing of inguinal white adipose tissue (iWAT) from kynurenine 3-monooxygenase (Kmo) knockout mice and wild-type littermates on chow and high-fat diets.

| PRJNA1163367 | ENA

Kynurenine 3-monooxygenase upregulates pluripotent genes through β-catenin and promotes triple-negative breast cancer progression

Project description:We used microarray to indentify KMO-regulated genes.

2020-05-06 | GSE145661 | GEO

The Kynurenine Pathway and Kynurenine 3-Monooxygenase Inhibitors.

Project description:Under normal physiological conditions, the kynurenine pathway (KP) plays a critical role in generating cellular energy and catabolizing tryptophan. Under inflammatory conditions, however, there is an upregulation of the KP enzymes, particularly kynurenine 3-monooxygenase (KMO). KMO has garnered much attention due to its production of toxic metabolites that have been implicated in many diseases and disorders. With many of these illnesses having an inadequate or modest treatment, there exists a need to develop KMO inhibitors that reduce the production of these toxic metabolites. Though prior efforts to find an appropriate KMO inhibitor were unpromising, the development of a KMO crystal structure has provided the opportunity for a rational structure-based design in the development of inhibitors. Therefore, the purpose of this review is to describe the kynurenine pathway, the kynurenine 3-monooxygenase enzyme, and KMO inhibitors and their potential candidacy for clinical use.

| S-EPMC8747024 | biostudies-literature

Modulation of Enzyme Activity in the Kynurenine Pathway by Kynurenine Monooxygenase Inhibition.

Project description:The kynurenine pathway is the major route for tryptophan metabolism in mammals. Several of the metabolites in the kynurenine pathway, however, are potentially toxic, particularly 3-hydroxykynurenine, 3-hydroxyanthranilic acid, and quinolinic acid. Quinolinic acid (QUIN) is an excitotoxic agonist at the NMDA receptor, and has been shown to be elevated in neurodegenerative diseases such as Alzheimer's Disease and Huntington's Disease. Thus, inhibitors of enzymes in the kynurenine pathway may be valuable to treat these diseases. Kynurenine monooxygenase (KMO) is the ideal target for an inhibitor, since inhibition of it would be expected to decrease the toxic metabolites and increase kynurenic acid (KynA), which is neuroprotective. The first generation of KMO inhibitors was based on structural analogs of the substrate, L-kynurenine. These compounds showed reduction of QUIN and increased KynA in vivo in rats. After the determination of the x-ray crystal structure of yeast KMO, inhibitor design has been facilitated. Benzisoxazoles with sub-nM binding to KMO have been developed recently. Some KMO ligands promote the reaction of NADPH with O2 without hydroxylation, resulting in uncoupled formation of H2O2. This potentially toxic side reaction should be avoided in the design of drugs targeting the kynurenine pathway for treatment of neurodegenerative disorders.

| S-EPMC6376250 | biostudies-literature

Structural basis of kynurenine 3-monooxygenase inhibition.

Project description:Inhibition of kynurenine 3-monooxygenase (KMO), an enzyme in the eukaryotic tryptophan catabolic pathway (that is, kynurenine pathway), leads to amelioration of Huntington's-disease-relevant phenotypes in yeast, fruitfly and mouse models, as well as in a mouse model of Alzheimer's disease. KMO is a flavin adenine dinucleotide (FAD)-dependent monooxygenase and is located in the outer mitochondrial membrane where it converts l-kynurenine to 3-hydroxykynurenine. Perturbations in the levels of kynurenine pathway metabolites have been linked to the pathogenesis of a spectrum of brain disorders, as well as cancer and several peripheral inflammatory conditions. Despite the importance of KMO as a target for neurodegenerative disease, the molecular basis of KMO inhibition by available lead compounds has remained unknown. Here we report the first crystal structure of Saccharomyces cerevisiae KMO, in the free form and in complex with the tight-binding inhibitor UPF 648. UPF 648 binds close to the FAD cofactor and perturbs the local active-site structure, preventing productive binding of the substrate l-kynurenine. Functional assays and targeted mutagenesis reveal that the active-site architecture and UPF 648 binding are essentially identical in human KMO, validating the yeast KMO-UPF 648 structure as a template for structure-based drug design. This will inform the search for new KMO inhibitors that are able to cross the blood-brain barrier in targeted therapies against neurodegenerative diseases such as Huntington's, Alzheimer's and Parkinson's diseases.

| S-EPMC3736096 | biostudies-literature

RNA sequencing analysis of hepatic transcriptome profiles in experimental nonalcoholic steatohepatitis

Project description:Two-month-old C57BL/6J male mice were placed on either chow diet or a diet enriched in high fat, cholesterol, and fructose (Research diet D09100301: 40 kcal% fat, 2% cholesterol, 20 kcal% fructose, HFCF diet) for 1 or 3 months. RNA-seq was used to analyze hepatic gene expression from mice on 1-month chow diet, 1-month HFCF diet, 3-month chow diet, and 3-month HFCF.

2019-12-10 | GSE135050 | GEO

Kynurenine 3-Monooxygenase: An Influential Mediator of Neuropathology.

Project description:Mounting evidence demonstrates that kynurenine metabolism may play an important pathogenic role in the development of multiple neurological and neuropsychiatric disorders. The kynurenine pathway consists of two functionally distinct branches that generate both neuroactive and oxidatively reactive metabolites. In the brain, the rate-limiting enzyme for one of these branches, kynurenine 3-monooxygenase (KMO), is predominantly expressed in microglia and has emerged as a pivotal point of metabolic regulation. KMO substrate and expression levels are upregulated by pro-inflammatory cytokines and altered by functional genetic mutations. Increased KMO metabolism results in the formation of metabolites that activate glutamate receptors and elevate oxidative stress, while recent evidence has revealed neurodevelopmental consequences of reduced KMO activity. Together, the evidence suggests that KMO is positioned at a critical metabolic junction to influence the development or trajectory of a myriad of neurological diseases. Understanding the mechanism(s) by which alterations in KMO activity are able to impair neuronal function, and viability will enhance our knowledge of related disease pathology and provide insight into novel therapeutic opportunities. This review will discuss the influence of KMO on brain kynurenine metabolism and the current understanding of molecular mechanisms by which altered KMO activity may contribute to neurodevelopment, neurodegenerative, and neuropsychiatric diseases.

| S-EPMC4542134 | biostudies-literature

Differentially expressed mRNA and circular RNA in HFD-fed or normal chow-diet-fed mice aortas

Project description:mRNA and Circular RNA sequencing data of aortas of ApoE-/- male mice fed with high fat diet or normal chow diet for 12 weeks.

2021-05-19 | GSE159379 | GEO

Gene expression in the liver, effect of maternal high-fat diet during or prior to pregnancy

Project description:The present study aimed to examine the effect of high-fat diet prior to pregnancy on the liver of mouse offspring. Female C57BL/6J mice were fed a normal chow (15.2% fat by energy) (CTR and CTR-PP groups) or a high-fat chow (31.2% fat by energy) (HFD and HFD-PP groups) for 3−4 weeks and then mated with male C57BL/6J mice fed normal chow. Some mothers continued on the same diet until pups reached 21 days of age (CTR and HFD), and others were fed the different chows from gestational day 0 (CTR-PP and HFD-PP) to determine the effects of a high-fat diet during the pre-pregnancy period in HFD-PP/CTR and HFD/CTR-PP comparisons.

2013-06-18 | GSE48014 | GEO

Significance of Kynurenine 3-Monooxygenase Expression in Colorectal Cancer.

Project description:Colorectal cancer (CRC) is a leading cause of cancer-related deaths. Because of the lack of reliable prognostic and predictive biomarkers for CRC, most patients are often diagnosed at a late stage. The tryptophan-kynurenine pathway plays a crucial role in promoting cancer progression. Kynurenine is considered an oncometabolite in colon cancer, and its downstream metabolites are also associated with CRC. Kynurenine 3-monooxygenase (KMO), a pivotal enzyme that catalyzes kynurenine metabolism, is essential for several cellular processes. In the current study, we explored the role of KMO in CRC. Immunohistochemical results showed that KMO was upregulated in CRC tissues relative to paired healthy tissue and polyps. Moreover, CRC patients with higher KMO expression were associated with higher metastasis and poorer survival rates. Knockdown of KMO decreased the expression of cancer stem cell markers, as well as the sphere-forming, migration, and invasion abilities of CRC cells. Additionally, blockade of the enzymatic activity of KMO using an inhibitor suppressed sphere formation and cell motility in CRC cells. These findings suggest the clinical relevance of KMO in CRC tumorigenesis and aggressiveness.

| S-EPMC8085544 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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