Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Knockdown of Ketohexokinase Versus Inhibition of Its Kinase Activity Exert Divergent Effects on Fructose Metabolism

ABSTRACT: Knockdown of Ketohexokinase Versus Inhibition of Its Kinase Activity Exert Divergent Effects on Fructose Metabolism

PROVIDER: PRJNA1166337 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR30826422.fastq.gz	Fastqsanger.gz
	SRR30826423.fastq.gz	Fastqsanger.gz
	SRR30826424.fastq.gz	Fastqsanger.gz
	SRR30826425.fastq.gz	Fastqsanger.gz
	SRR30826426.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 16

Similar Datasets

Knockdown of Ketohexokinase Versus Inhibition of Its Kinase Activity Exert Divergent Effects on Fructose Metabolism

Project description:Excessive fructose intake is a risk factor for the development of obesity and its complications. Targeting ketohexokinase (KHK), the first enzyme of fructose metabolism, has been investigated for the management of MASLD. We compared the effects of systemic, small molecule inhibitor of KHK enzymatic activity to hepatocyte-specific, GalNAc-siRNA mediated knockdown of KHK in mice on a HFD. We measured KHK enzymatic activity, extensively quantified glycogen accumulation, performed RNAseq analysis, and enumerated hepatic metabolites using mass spectrometry. Both KHK siRNA and KHK inhibitor led to an improvement in liver steatosis, however, via substantially different mechanisms. KHK knockdown decreased the de novo lipogenesis pathway, whereas the inhibitor increased the fatty acid oxidation pathway. Moreover, KHK knockdown completely prevented hepatic fructolysis and improved glucose tolerance. Conversely, the KHK inhibitor only partially reduced fructolysis, but it also targeted triokinase, mediating the third step of fructolysis. This leads to the accumulation of fructose-1 phosphate, resulting in glycogen accumulation, hepatomegaly, and impaired glucose tolerance. Overexpression of wild-type, but not kinase-dead KHK in cultured hepatocytes increased hepatocyte injury and glycogen accumulation when treated with fructose. The differences between KHK inhibition and knockdown are, in part, explained by the kinase-dependent and independent effects of KHK on hepatic metabolism.

2024-11-14 | GSE278322 | GEO

Knockdown of ketohexokinase versus inhibition of its kinase activity exert divergent effects on fructose metabolism.

Project description: Not available

| S-EPMC11623947 | biostudies-literature

PFKFB3 inhibits fructose metabolism in pulmonary microvascular endothelial cells

Project description:We hypothesized that PFKFB3 inhibits fructose metabolism in pulmonary microvascular endothelial cells (PMVECs) and found that PFKFB3 knockout cells survive better than wild type cells in fructose-rich media, more so under hypoxia. Our findings indicate that PFKFB3 is a molecular switch that controls glucose versus fructose utilization in glycolysis and help to better understand lung endothelial cell metabolism during respiratory failure.

2023-08-01 | GSE230660 | GEO

Transcriptome data of Huh7 cells treated with glucose or fructose

Project description:The transcriptome sequencing compared gene expression differences in Huh7 cells treated with glucose versus fructose. At the nutrient level, fructose treatment alone did not induce severe endoplasmic reticulum (ER) stress compared to glucose. However, upon KHK-C overexpression, fructose treatment led to significant ER stress. At the genetic level, glucose treatment did not trigger ER stress even with KHK-C overexpression, whereas fructose treatment under the same conditions resulted in pronounced ER stress. Additionally, Aldob knockdown further exacerbated ER stress. In summary, our findings suggest that in Huh7 cells, KHK-C-mediated phosphorylation of fructose into fructose-1-phosphate (F1P) leads to intracellular F1P accumulation, which drives severe ER stress.

2026-03-31 | GSE293320 | GEO

Human tolerogenic dendritic cell subtypes exert divergent effects on induction of cytotoxic CD4+ T cells

Project description:Human tolerogenic dendritic cell subtypes exert divergent effects on induction of cytotoxic CD4+ T cells

| PRJNA1381536 | ENA

Divergent principles specifying inflammatory versus antiviral transcriptional programs in dendritic cells

Project description:Divergent principles specifying inflammatory versus antiviral transcriptional programs in dendritic cells

| PRJNA417853 | ENA

6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 is essential for p53-null cancer cells

Project description:The bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-4 (PFKFB4) controls metabolic flux through allosteric regulation of glycolysis. Here we show that p53 regulates the expression of PFKFB4 and that p53-deficient cancer cells are highly dependent on the function of this enzyme. We found that p53 down-regulates PFKFB4 expression by binding to its promoter and mediating transcriptional repression via histone deacetylases. Depletion of PFKFB4 from p53 deficient cancer cells increased levels of the allosteric regulator fructose 2,6-bisphophate, leading to increased glycolytic activity but decreased routing of metabolites through the oxidative arm of the pentose phosphate pathway. PFKFB4 was also required to support the synthesis and regeneration of nicotinamide adenine dinucleotide phosphate (NADPH) in p53 deficient cancer cells. Moreover, depletion of PFKFB4 attenuated cellular biosynthetic activity and resulted in the accumulation of reactive oxygen species and cell death in the absence of p53. Finally, silencing of PFKFB4 induced apoptosis in p53 deficient cancer cells in vivo and interfered with tumour growth. These results demonstrate that PFKFB4 is essential to support anabolic metabolism in p53-deficient cancer cells and suggest that inhibition of PFKFB4 could be an effective strategy for cancer treatment.

2017-04-03 | GSE89110 | GEO

Polyphenols protection against fructose overload

Project description:To decipher the beneficial effects of Polyphenols on health, healthy volunteers were randomized into two groups and were submitted to either a red grape polyphenol rich extract supplemented diet (PP) or a placebo diet (PCB) during 8 weeks. Then they were submitted to a fructose load (3g/kg Fat Free Mass/day) during 7 days. Muscle biopsies were taken before the protocol, 8 weeks after PP or PCB diet and after the 7 days fructose load. We have employed whole genome microarray expression profiling as a discovery platform to identify genes regulated by fructose and to identify the mechanism of action of Polyphenols. Healthy volunteers were randomized into two groups and were submitted to either a red grape polyphenol rich extract supplemented diet (PP) or a placebo diet (PCB) during 8 weeks. Then they were submitted to a fructose load (3g/kg Fat Free Mass/day) during 7 days. Muscle biopsies were taken before the protocol, 8 weeks after PP or PCB diet and after the 7 days fructose load. We have employed whole genome microarray expression profiling as a discovery platform to identify genes regulated by fructose and to identify the mechanism of action of Polyphenols. Ten biological replicates were processed for PP diet, nine for PCB diet.

2013-02-04 | E-GEOD-35764 | biostudies-arrayexpress

A Pilot Study to Determine Fructose Uptake by Primary Human Colorectal Tumors

Project description:This proposed study is designed to investigate the specific uptake of fructose by human colorectal tumors. In this study, subjects with colorectal cancer undergoing surgery will receive an oral sugar solution containing fructose or xylose prior to surgery. The tumor will then be resected, and a portion of the tissue will be used to measure the abundance of fructose and xylose. The study hypothesis is that the tumors will take up fructose sugar but not xylose sugar. A comparison of the sugar uptake between the tumor and normal tissues from the adjacent intestinal epithelium and smooth muscle and the liver will be conducted. This proposal will confirm that human colorectal cancer tumors can directly absorb dietary sugars, which has never been demonstrated.

| 2396702 | ecrin-mdr-crc

Transcriptome analysis of the pfkB1 deletion mutant cultivated with glucose or fructose

Project description:In the analysis of a carbohydrate metabolite pathway, we found that a mutant strain of Corynebacterium glutamicum deficient in pfkB1, which encodes fructose-1-phosphate kinase, showed interesting characteristics. After aerobically cultivated with fructose as a carbon source, this mutant consumed glucose and produced lactate more than 2-fold as compared with the wild-type under conditions of oxygen deprivation. This considerably higher fermentation capacity was unique for the combination of the pfkB1 deletion and fructose cultivation. On the basis of the metabolome and transcriptome analyses, we identified marked intracellular accumulation of fructose-1-phosphate and significant upregulation of several genes related to the phosphoenolpyruvate:carbohydrate phosphotransferase system, glycolysis, and organic acid synthesis in this strain. Therefore, the considerably enhanced glucose consumption and organic acid production presumably resulted from a relief of transcriptional repression driven by global regulator SugR owing to the accumulated fructose-1-phosphate. Furthermore, we demonstrated that engineered strains overexpressing the above upregulated genes showed enhanced glucose consumption and organic acid production. The ppc deletion mutant of the engineered strain consumed 1,250 mM glucose and produced 2,390 mM lactate in 48 h under oxygen deprivation, which are 2.6- and 2.7-fold higher than the corresponding parameters of the ppc-deleted wild-type.

2016-11-28 | GSE83383 | GEO

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