Summary of Study ST003105

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001928. The data can be accessed directly via it's Project DOI: 10.21228/M8HB1C This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST003105
Study TitleActivation of GFRAL+ Neurons Induces Hypothermia and Glucoregulatory Responses Associated with Nausea and Torpor
Study SummaryGFRAL-expressing neurons actuate aversion and nausea, are targets for obesity treatment and may mediate metformin effects by long-term GDF15-GFRAL agonism. If GFRAL+ neurons acutely regulate glucose and energy homeostasis is however underexplored. Here, we report that cell-specific activation of GFRAL+ neurons using a variety of techniques causes a torpor-like state, including hypothermia, the release of stress hormones, a shift from glucose to lipid oxidation, and impaired insulin sensitivity, glucose tolerance and skeletal muscle glucose uptake but augmented glucose uptake in visceral fat. Metabolomic analysis of blood and transcriptomics of muscle and fat indicate alterations in ketogenesis, insulin signaling, adipose tissue differentiation and mitogenesis, and energy fluxes. Our findings reveal that acute GFRAL+ neuron activation induces endocrine and gluco- and thermoregulatory responses associated with nausea and torpor. While chronic activation of GFRAL signaling promotes weight loss in obesity, these results show that acute activation of GFRAL+ neurons causes hypothermia and hyperglycemia.
Institute
University of Gothenburg
Last NameRuud
First NameJohan
AddressMedicinaregatan 11
Emailjohan.ruud@gu.se
Phone+46766186879
Submit Date2024-02-19
Raw Data AvailableYes
Raw Data File Type(s)fid
Analysis Type DetailNMR
Release Date2024-03-18
Release Version1
Johan Ruud Johan Ruud
https://dx.doi.org/10.21228/M8HB1C
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR001928
Project DOI:doi: 10.21228/M8HB1C
Project Title:Activation of GFRAL+ Neurons Induces Hypothermia and Glucoregulatory Responses Associated with Nausea and Torpor
Project Summary:GFRAL-expressing neurons actuate aversion and nausea, are targets for obesity treatment and may mediate metformin effects by long-term GDF15-GFRAL agonism. If GFRAL+ neurons acutely regulate glucose and energy homeostasis is however underexplored. Here, we report that cell-specific activation of GFRAL+ neurons using a variety of techniques causes a torpor-like state, including hypothermia, the release of stress hormones, a shift from glucose to lipid oxidation, and impaired insulin sensitivity, glucose tolerance and skeletal muscle glucose uptake but augmented glucose uptake in visceral fat. Metabolomic analysis of blood and transcriptomics of muscle and fat indicate alterations in ketogenesis, insulin signaling, adipose tissue differentiation and mitogenesis, and energy fluxes. Our findings reveal that acute GFRAL+ neuron activation induces endocrine and gluco- and thermoregulatory responses associated with nausea and torpor. While chronic activation of GFRAL signaling promotes weight loss in obesity, these results show that acute activation of GFRAL+ neurons causes hypothermia and hyperglycemia.
Institute:University of Gothenburg
Last Name:Ruud
First Name:Johan
Address:Medicinaregatan 11
Email:johan.ruud@gu.se
Phone:+46766186879

Subject:

Subject ID:SU003220
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090
Species Group:Mammals

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Sample source Genotype
SA33362030Plasma Transgenic
SA33362128Plasma Transgenic
SA33362254Plasma Transgenic
SA33362324Plasma Transgenic
SA33362436Plasma Transgenic
SA33362542Plasma Transgenic
SA33362640Plasma Transgenic
SA33362746Plasma Transgenic
SA33362852Plasma Transgenic
SA33362958Plasma Transgenic
SA33363062Plasma Transgenic
SA3336314Plasma Transgenic
SA33363220Plasma Transgenic
SA33363312Plasma Transgenic
SA33363418Plasma Transgenic
SA33363516Plasma Transgenic
SA33363648Plasma Wild-type
SA33363756Plasma Wild-type
SA33363850Plasma Wild-type
SA33363960Plasma Wild-type
SA33364064Plasma Wild-type
SA33364134Plasma Wild-type
SA33364214Plasma Wild-type
SA33364310Plasma Wild-type
SA3336448Plasma Wild-type
SA3336456Plasma Wild-type
SA33364622Plasma Wild-type
SA33364726Plasma Wild-type
SA33364838Plasma Wild-type
SA3336492Plasma Wild-type
SA33365032Plasma Wild-type
SA33365144Plasma Wild-type
Showing results 1 to 32 of 32

Collection:

Collection ID:CO003213
Collection Summary:Blood was collected in EDTA-coated tubes, and plasma was obtained through centrifugation (7000 x g, 7 min, 4°C), snap frozen in liquid nitrogen and stored at -80°C until further use.
Sample Type:Blood (plasma)

Treatment:

Treatment ID:TR003229
Treatment Summary:Control mice (wild-type) and mice expressing hM3Dq in GFRAL neurons (transgenic) were given CNO (1 mg/kg) i.p. and bled 6 hours later for NMR metabolomics.

Sample Preparation:

Sampleprep ID:SP003226
Sampleprep Summary:Plasma was thawed at room temperature for 15 min before transferring 150 µl to pre-washed ultrafiltration tubes (Amicon Ultra 0.5 ml, 3k MWCO, Merck Millipore) which were spun at 14000 x g, at 4°C for 90 min. 90 µl of each filtrate was mixed with 90 µl buffer (75 mM sodium phosphate pH 7.4, 0.1% w/v sodium azide, 3.66 mM 3-(trimethylsilyl)propionic-2,2,3,3-d4 acid (TSPd4), in 20% v/v D2O) and transferred to 3 mm SampleJet NMR-tubes.

Analysis:

Analysis ID:AN005084
Analysis Type:NMR
Num Factors:2
Num Metabolites:49
Units:mM

NMR:

NMR ID:NM000276
Analysis ID:AN005084
Instrument Name:Bruker Neo
Instrument Type:FT-NMR
NMR Experiment Type:1D-1H
Spectrometer Frequency:599.75 MHz
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