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.

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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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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.
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