Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Combinatorial targeting of the miR-379/miR-410 cluster normalizes glucose and lipid homeostasis in male models of diabetes and obesity

ABSTRACT: The miR-379/miR-410 cluster, belonging to the Dlk1-Dio3 locus, is the largest cluster of miRNAs in mammals. Most of its components are predicted to regulate insulin signaling, and we found consistent upregulation of the cluster in the livers of obese subjects as well as of different experimental models of insulin resistance. We have engineered a tool, a TuD, able to target two microRNAs from the cluster in a liver-specific manner. As a result, the cluster is repressed, which activates insulin signaling in the liver and leads to enhanced hepatic insulin sensitivity and reduced hepatic glucose output. This dataset includes transcriptomics data from liver tissue of young male mice carrying hepatic-specific expression of a TuD inhibitor able to repress the miR-379/miR-410 cluster (n=6) or a negative control sequence (n=5).

ORGANISM(S): Mus musculus

PROVIDER: GSE304566 | GEO | 2026/07/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Hepatic transcriptome of mice with a deletion of the miR-379/miR-410 cluster at P1

Project description:In placental mammals, adaptation to extra-uterine life requires complex metabolic adjustments linked to the abrupt transition from the transplacental transfer of glucose toward the use of fat originating from the motherM-bM-^@M-^Ys milk as a major energy source. The study of a novel knock-out mouse model led us to identify the biological roles of the miR-379/miR-410 cluster at the imprinted Dlk1-Dio3 region during this metabolic transition. The miR-379/miR-410 cluster is the largest mammalian-specific miRNA cluster composed of 39 pre-miRNA and expressed from the maternally-inherited allele. We unexpectedly found that ~ 35% of heterozygous neonates with a maternal - but not paternal - deletion of the entire 40kb-long miRNA cluster die shortly after birth due to defects in the maintenance of energy homeostasis, as evidenced by impaired hepatic glycogenolysis, gluconeogenesis and ketogenesis. This maladaptive metabolic response is accompanied by profound changes in the neonatal hepatic gene expression program, notably a decrease in the activation of a large set of metabolic genes linked to lipid metabolism. Our study unveils essential roles for the miR-379/miR-410 cluster at the transition from fetal to postnatal life, revealing new layers of RNA-mediated gene regulation at the Dlk1-Dio3 domain that impose parent-of-origin effects on postnatal metabolic functions. Liver gene expression at P1 was measured in neonates with a maternally-inherited deletion of the miR-379/miR-410 cluster (KO) and compared to that of wild-type littermates (n=5). KO_normoglycemic and KO_hypoglycemic individuals correspond to mutant pups wild mild hypoglycemia (n=3) and with severe hypoglycemia (n =7), respectively.

2014-08-22 | E-GEOD-57112 | biostudies-arrayexpress

Hepatic transcriptome of mice with a deletion of the miR-379/miR-410 cluster at E19.5 and P0

Project description:In placental mammals, adaptation to extra-uterine life requires complex metabolic adjustments linked to the abrupt transition from the transplacental transfer of glucose toward the use of fat originating from the motherM-bM-^@M-^Ys milk as a major energy source. The study of a novel knock-out mouse model led us to identify the biological roles of the miR-379/miR-410 cluster at the imprinted Dlk1-Dio3 region during this metabolic transition. The miR-379/miR-410 cluster is the largest mammalian-specific miRNA cluster composed of 39 pre-miRNA and expressed from the maternally-inherited allele. We unexpectedly found that ~ 35% of heterozygous neonates with a maternal - but not paternal - deletion of the entire 40kb-long miRNA cluster die shortly after birth due to defects in the maintenance of energy homeostasis, as evidenced by impaired hepatic glycogenolysis, gluconeogenesis and ketogenesis. This maladaptive metabolic response is accompanied by profound changes in the neonatal hepatic gene expression program, notably a decrease in the activation of a large set of metabolic genes linked to lipid metabolism. Our study unveils essential roles for the miR-379/miR-410 cluster at the transition from fetal to postnatal life, revealing new layers of RNA-mediated gene regulation at the Dlk1-Dio3 domain that impose parent-of-origin effects on postnatal metabolic functions. Liver gene expression was measured in mice with a maternally-inherited deletion of the miR-379/miR-410 cluster (KO) and in wild-type littermates (WT) at embryonic day E19.5 (n=3 per genotype) and on the day of birth (P0, n=4 WT and 5 KO).

2014-08-22 | E-GEOD-47156 | biostudies-arrayexpress

Hepatic transcriptome of mice with a deletion of the miR-379/miR-410 cluster obtained 4h following a caesarean at embryonic day E19.5

Project description:In placental mammals, adaptation to extra-uterine life requires complex metabolic adjustments linked to the abrupt transition from the transplacental transfer of glucose toward the use of fat originating from the motherM-bM-^@M-^Ys milk as a major energy source. The study of a novel knock-out mouse model led us to identify the biological roles of the miR-379/miR-410 cluster at the imprinted Dlk1-Dio3 region during this metabolic transition. The miR-379/miR-410 cluster is the largest mammalian-specific miRNA cluster composed of 39 pre-miRNA and expressed from the maternally-inherited allele. We unexpectedly found that ~ 35% of heterozygous neonates with a maternal - but not paternal - deletion of the entire 40kb-long miRNA cluster die shortly after birth due to defects in the maintenance of energy homeostasis, as evidenced by impaired hepatic glycogenolysis, gluconeogenesis and ketogenesis. This maladaptive metabolic response is accompanied by profound changes in the neonatal hepatic gene expression program, notably a decrease in the activation of a large set of metabolic genes linked to lipid metabolism. Our study unveils essential roles for the miR-379/miR-410 cluster at the transition from fetal to postnatal life, revealing new layers of RNA-mediated gene regulation at the Dlk1-Dio3 domain that impose parent-of-origin effects on postnatal metabolic functions. Liver gene expression was measured in mice with a maternally-inherited deletion of the miR-379/miR-410 cluster and in wild-type littermates at embryonic day E19.5, 4h following the caesarean delivery (n=4 biological replicates per genotype)

2014-08-22 | E-GEOD-47155 | biostudies-arrayexpress

Hepatic transcriptome of mice with a deletion of the miR-379/miR-410 cluster at P1

Project description:In placental mammals, adaptation to extra-uterine life requires complex metabolic adjustments linked to the abrupt transition from the transplacental transfer of glucose toward the use of fat originating from the mother’s milk as a major energy source. The study of a novel knock-out mouse model led us to identify the biological roles of the miR-379/miR-410 cluster at the imprinted Dlk1-Dio3 region during this metabolic transition. The miR-379/miR-410 cluster is the largest mammalian-specific miRNA cluster composed of 39 pre-miRNA and expressed from the maternally-inherited allele. We unexpectedly found that ~ 35% of heterozygous neonates with a maternal - but not paternal - deletion of the entire 40kb-long miRNA cluster die shortly after birth due to defects in the maintenance of energy homeostasis, as evidenced by impaired hepatic glycogenolysis, gluconeogenesis and ketogenesis. This maladaptive metabolic response is accompanied by profound changes in the neonatal hepatic gene expression program, notably a decrease in the activation of a large set of metabolic genes linked to lipid metabolism. Our study unveils essential roles for the miR-379/miR-410 cluster at the transition from fetal to postnatal life, revealing new layers of RNA-mediated gene regulation at the Dlk1-Dio3 domain that impose parent-of-origin effects on postnatal metabolic functions.

2014-08-22 | GSE57112 | GEO

Hepatic transcriptome of mice with a deletion of the miR-379/miR-410 cluster at E19.5 and P0

Project description:In placental mammals, adaptation to extra-uterine life requires complex metabolic adjustments linked to the abrupt transition from the transplacental transfer of glucose toward the use of fat originating from the mother’s milk as a major energy source. The study of a novel knock-out mouse model led us to identify the biological roles of the miR-379/miR-410 cluster at the imprinted Dlk1-Dio3 region during this metabolic transition. The miR-379/miR-410 cluster is the largest mammalian-specific miRNA cluster composed of 39 pre-miRNA and expressed from the maternally-inherited allele. We unexpectedly found that ~ 35% of heterozygous neonates with a maternal - but not paternal - deletion of the entire 40kb-long miRNA cluster die shortly after birth due to defects in the maintenance of energy homeostasis, as evidenced by impaired hepatic glycogenolysis, gluconeogenesis and ketogenesis. This maladaptive metabolic response is accompanied by profound changes in the neonatal hepatic gene expression program, notably a decrease in the activation of a large set of metabolic genes linked to lipid metabolism. Our study unveils essential roles for the miR-379/miR-410 cluster at the transition from fetal to postnatal life, revealing new layers of RNA-mediated gene regulation at the Dlk1-Dio3 domain that impose parent-of-origin effects on postnatal metabolic functions.

2014-08-22 | GSE47156 | GEO

Hepatic transcriptome of mice with a deletion of the miR-379/miR-410 cluster obtained 4h following a caesarean at embryonic day E19.5

Project description:In placental mammals, adaptation to extra-uterine life requires complex metabolic adjustments linked to the abrupt transition from the transplacental transfer of glucose toward the use of fat originating from the mother’s milk as a major energy source. The study of a novel knock-out mouse model led us to identify the biological roles of the miR-379/miR-410 cluster at the imprinted Dlk1-Dio3 region during this metabolic transition. The miR-379/miR-410 cluster is the largest mammalian-specific miRNA cluster composed of 39 pre-miRNA and expressed from the maternally-inherited allele. We unexpectedly found that ~ 35% of heterozygous neonates with a maternal - but not paternal - deletion of the entire 40kb-long miRNA cluster die shortly after birth due to defects in the maintenance of energy homeostasis, as evidenced by impaired hepatic glycogenolysis, gluconeogenesis and ketogenesis. This maladaptive metabolic response is accompanied by profound changes in the neonatal hepatic gene expression program, notably a decrease in the activation of a large set of metabolic genes linked to lipid metabolism. Our study unveils essential roles for the miR-379/miR-410 cluster at the transition from fetal to postnatal life, revealing new layers of RNA-mediated gene regulation at the Dlk1-Dio3 domain that impose parent-of-origin effects on postnatal metabolic functions.

2014-08-22 | GSE47155 | GEO

micro RNA-379 couples glucocorticoid hormones to metabolic dysfunction in diabesity

Project description:In metabolic control, GC signaling acts as a major counter-regulatory system against insulin action, and aberrantly elevated GC activity is tightly linked to major components of the so-called Metabolic Syndrome, including obesity, insulin resistance, hyperglycemia, and systemic dyslipidemia. Here we identify the hepatic induction of the conserved microRNA (miR)-379/410 genomic cluster as a key component of GC/GR-driven metabolic dysfunction in “diabesity” Microarray data were utilized to screened for differentially regulated miRNAs between wt and db/db and between wt and GR Knockdown mice

2014-10-15 | GSE55245 | GEO

micro RNA-379 couples glucocorticoid hormones to metabolic dysfunction in diabesity

Project description:In metabolic control, GC signaling acts as a major counter-regulatory system against insulin action, and aberrantly elevated GC activity is tightly linked to major components of the so-called Metabolic Syndrome, including obesity, insulin resistance, hyperglycemia, and systemic dyslipidemia. Here we identify the hepatic induction of the conserved microRNA (miR)-379/410 genomic cluster as a key component of GC/GR-driven metabolic dysfunction in M-bM-^@M-^\diabesityM-bM-^@M-^] Microarray data were utilized to screened for differentially regulated miRNAs between wt and db/db and between wt and GR Knockdown mice For wt vs. db/db: mice were fasted for 24 hours and refed for 6 hours; For GR-dependent miRNAs: mice were treated with rAAV delivering either control or GR-directed miRNA for the knockdown of the GR specifically in the liver.

2014-10-15 | E-GEOD-55245 | biostudies-arrayexpress

Hepatic transcriptome of mice with a deletion of the miR-379/miR-410 cluster

Project description:Hepatic transcriptome of mice with a deletion of the miR-379/miR-410 cluster

| PRJNA204589 | ENA

miRNA-mediated inhibition of an actomyosin network in hippocampal pyramidal neurons restricts sociability in adult male mice

Project description:We recently reported that the loss of the microRNA cluster miR-379-410 leads to hypersocial behavior and anxiety in mice. With this study, we show that ablating miR-379-410 in excitatory neurons of the postnatal mouse hippocampus recapitulates hypersociability, but not anxiety. At the cellular level, miR-379-410 loss in excitatory neurons leads to increased excitatory synaptic transmission and upregulation of an actomyosin gene network. Re-expression of three cluster miRNAs, as well as pharmacological inhibition of the actomyosin activator ROCK, was sufficient to reinstate normal sociability in miR-379-410 knockout mice. Our results unveil a novel microRNA-actomyosin pathway involved in the control of sociability.

2024-05-03 | GSE247439 | 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