Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Truncation of Pik3r1 Causes Severe Insulin Resistance Uncoupled From Obesity and Dyslipidaemia by Increased Energy Expenditure

ABSTRACT: Truncation of Pik3r1 Causes Severe Insulin Resistance Uncoupled From Obesity and Dyslipidaemia by Increased Energy Expenditure

PROVIDER: PRJNA642642 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR12103700.fastq.gz	Fastqsanger.gz
	SRR12103701.fastq.gz	Fastqsanger.gz
	SRR12103702.fastq.gz	Fastqsanger.gz
	SRR12103703.fastq.gz	Fastqsanger.gz
	SRR12103704.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 72

Similar Datasets

GDF15 and energy expenditure

Project description:GDF15 and energy expenditure

| PRJNA957834 | ENA

Truncation of Pik3r1 causes severe insulin resistance uncoupled from obesity and dyslipidaemia by increased energy expenditure.

Project description:ObjectiveInsulin signalling via phosphoinositide 3-kinase (PI3K) requires PIK3R1-encoded regulatory subunits. C-terminal PIK3R1 mutations cause SHORT syndrome, as well as lipodystrophy and insulin resistance (IR), surprisingly without fatty liver or metabolic dyslipidaemia. We sought to investigate this discordance.MethodsThe human pathogenic Pik3r1 Y657∗ mutation was knocked into mice by homologous recombination. Growth, body composition, bioenergetic and metabolic profiles were investigated on chow and high-fat diet (HFD). We examined adipose and liver histology, and assessed liver responses to fasting and refeeding transcriptomically.ResultsLike humans with SHORT syndrome, Pik3r1WT/Y657∗ mice were small with severe IR, and adipose expansion on HFD was markedly reduced. Also as in humans, plasma lipid concentrations were low, and insulin-stimulated hepatic lipogenesis was not increased despite hyperinsulinemia. At odds with lipodystrophy, however, no adipocyte hypertrophy nor adipose inflammation was found. Liver lipogenic gene expression was not significantly altered, and unbiased transcriptomics showed only minor changes, including evidence of reduced endoplasmic reticulum stress in the fed state and diminished Rictor-dependent transcription on fasting. Increased energy expenditure, which was not explained by hyperglycaemia nor intestinal malabsorption, provided an alternative explanation for the uncoupling of IR from dyslipidaemia.ConclusionsPik3r1 dysfunction in mice phenocopies the IR and reduced adiposity without lipotoxicity of human SHORT syndrome. Decreased adiposity may not reflect bona fide lipodystrophy, but rather, increased energy expenditure, and we suggest that further study of brown adipose tissue in both humans and mice is warranted.

| S-EPMC7385515 | biostudies-literature

Truncation of Pik3r1 Causes Severe Insulin Resistance Uncoupled From Obesity and Dyslipidaemia by Increased Energy Expenditure

Project description:Both PIK3R1(Y657X) mutant and wild-type C57Bl/6J mice were maintained on chow until 16 weeks old, at which time they were fasted for 16 hours and then refed chow for 6 hours. The tissues were harvested and snap-frozen at three time points: chow diet before overnight fast (ad libitum chow, ALC), after 16 hour fast (overnight fast, ONF), and after 6 hour refeeding (refed 6 hours, RF6).

2020-06-30 | GSE153431 | GEO

Proteomic Analysis of Human Brown Adipose Tissue Reveals Utilization of Coupled and Uncoupled Energy Expenditure Pathways

Project description:Human brown adipose tissue (BAT) has become an attractive target to combat the current epidemical spread of obesity and its associated co-morbidities. Currently, information on its functional role is primarily derived from rodent studies. Here, we present the first comparative proteotype analysis of primary human brown adipose tissue versus adjacent white adipose tissue, which reveals significant quantitative differences in protein abundances and in turn differential functional capabilities. The majority of the 318 proteins with increased abundance in BAT are associated with mitochondrial metabolism and confirm the increased oxidative capacity. In addition to uncoupling protein 1 (UCP1), the main functional effector for uncoupled respiration, we also detected the mitochondrial creatine kinases (CKMT1A/B, CKMT2), as effective modulators of ATP synthase coupled respiration, to be exclusively expressed in BAT. The abundant expression and utilization of both energy expenditure pathways in parallel highlights the complex functional involvement of BAT in human physiology.

2016-07-21 | PXD003843 | Pride

An insulin-stimulated proteolytic mechanism links energy expenditure with glucose uptake

Project description:Mechanisms to coordinately regulate oxidative metabolism and glucose transport into cells are not well described. In muscle and fat, insulin mobilizes GLUT4 glucose transporters to the cell surface in part by stimulating the site-specific endoproteolytic cleavage of TUG proteins. Here, we show that the TUG C-terminal cleavage product enters the nucleus, binds the transcriptional 30 regulators PGC-1a and PPARg, and increases oxidative metabolism, thermogenic protein expression, and energy expenditure. The PPARg2 Pro12Gly polymorphism, which confers reduced diabetes risk, enhances TUG binding. The TUG cleavage product stabilizes PGC-1a, so that both proteins are susceptible to an Ate1 arginyltransferase -dependent degradation mechanism. We conclude that TUG cleavage coordinates energy expenditure with glucose 35 uptake, and that alterations in this pathway may contribute to metabolic disease.

2020-07-23 | GSE134846 | GEO

A Prader-Willi locus lncRNA cloud modulates diurnal genes and energy expenditure.

Project description:Prader-Willi syndrome (PWS), a genetic cause of childhood obesity, is characterized by intellectual disabilities and sleep abnormalities. PWS-causing deletions include a neuronal long, non-coding RNA (lncRNA) processed into small nucleolar RNAs and a spliced lncRNA,116HG. We show that 116HG forms a subnuclear RNA cloud that co-purifies with the transcriptional activator RBBP5 and active metabolic genes, remains tethered to the site of its transcription and increases in size in postnatal neurons. Snord116del mice lacking 116HG exhibited increased energy expenditure corresponding to dysregulation of diurnally expressed Mtor and circadian genes Clock, Cry1, and Per2. Genomic and metabolic analyses demonstrate altered diurnal energy regulation in the Snord116del mouse cortex and link the loss of 116HG to the energy imbalance observed in PWS. Examination of lncRNA binding sites by ChIRP-seq using an oligo-based purification method from WT and Snord116del (+/-) mouse brain with specific and nonspecific control oligos. Transcript abundance levels by RNA-seq analysis of 3 adult WT and 2 adult Snord116del (+/-) mouse brain cortices at Zt+6 and 2 adult WT and 2 adult Snord116del (+/-) mouse brain cortices at Zt+16.

2013-06-20 | E-GEOD-43575 | biostudies-arrayexpress

An insulin-stimulated proteolytic mechanism links energy expenditure with glucose uptake

Project description:An insulin-stimulated proteolytic mechanism links energy expenditure with glucose uptake

| PRJNA556648 | ENA

A Prader-Willi locus lncRNA cloud modulates diurnal genes and energy expenditure.

2013-06-20 | GSE43575 | GEO

Determining Energy Needs in Colorectal Cancer

Project description:This is an observational study to assess the determinants of energy expenditure in cancer, and how those change throughout the disease trajectory. The investigators hypothesize that skeletal muscle will be the primary determinant of energy expenditure throughout the disease trajectory.

| 2242749 | ecrin-mdr-crc

Astrocytic circadian clock control of energy expenditure by transcriptional stress responses in the ventromedial hypothalamus

Project description:Mice carrying a mutation which deletes Bmal1 in Gfap-expressing astrocytes, and control animals were fed either a standard diet or a high fat diet for 16 weeks. Conditional deletion of Bmal1 in Gfap cells decreased weight gain and increased energy expenditure under high fat diet, hence the transcriptome of Brown Adipose Tissue (BAT) and Ventromedial Hypothalamus (VMH) were obtained.

2023-04-12 | GSE203125 | 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