{
"METABOLOMICS WORKBENCH":{"STUDY_ID":"ST003105","ANALYSIS_ID":"AN005084","VERSION":"1","CREATED_ON":"February 19, 2024, 5:35 am"},

"PROJECT":{"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"},

"STUDY":{"STUDY_TITLE":"Activation of GFRAL+ Neurons Induces Hypothermia and Glucoregulatory Responses Associated with Nausea and Torpor","STUDY_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_TYPE":"Mammal","SUBJECT_SPECIES":"Mus musculus","TAXONOMY_ID":"10090"},
"SUBJECT_SAMPLE_FACTORS":[
{
"Subject ID":"blood1_cage1",
"Sample ID":"2",
"Factors":{"Sample source":"Plasma","Genotype":"Wild-type"},
"Additional sample data":{"Treatment":"CNO_6h","RAW_FILE_NAME":"2"}
},
{
"Subject ID":"blood1_cage3",
"Sample ID":"4",
"Factors":{"Sample source":"Plasma","Genotype":"Transgenic"},
"Additional sample data":{"Treatment":"CNO_6h","RAW_FILE_NAME":"4"}
},
{
"Subject ID":"blood1_cage4",
"Sample ID":"6",
"Factors":{"Sample source":"Plasma","Genotype":"Wild-type"},
"Additional sample data":{"Treatment":"CNO_6h","RAW_FILE_NAME":"6"}
},
{
"Subject ID":"blood1_cage5",
"Sample ID":"8",
"Factors":{"Sample source":"Plasma","Genotype":"Wild-type"},
"Additional sample data":{"Treatment":"CNO_6h","RAW_FILE_NAME":"8"}
},
{
"Subject ID":"blood1_cage6",
"Sample ID":"10",
"Factors":{"Sample source":"Plasma","Genotype":"Wild-type"},
"Additional sample data":{"Treatment":"CNO_6h","RAW_FILE_NAME":"10"}
},
{
"Subject ID":"blood1_cage8",
"Sample ID":"12",
"Factors":{"Sample source":"Plasma","Genotype":"Transgenic"},
"Additional sample data":{"Treatment":"CNO_6h","RAW_FILE_NAME":"12"}
},
{
"Subject ID":"blood1_cage9",
"Sample ID":"14",
"Factors":{"Sample source":"Plasma","Genotype":"Wild-type"},
"Additional sample data":{"Treatment":"CNO_6h","RAW_FILE_NAME":"14"}
},
{
"Subject ID":"blood1_cage10",
"Sample ID":"16",
"Factors":{"Sample source":"Plasma","Genotype":"Transgenic"},
"Additional sample data":{"Treatment":"CNO_6h","RAW_FILE_NAME":"16"}
},
{
"Subject ID":"blood1_cage13",
"Sample ID":"18",
"Factors":{"Sample source":"Plasma","Genotype":"Transgenic"},
"Additional sample data":{"Treatment":"CNO_6h","RAW_FILE_NAME":"18"}
},
{
"Subject ID":"blood1_cage14",
"Sample ID":"20",
"Factors":{"Sample source":"Plasma","Genotype":"Transgenic"},
"Additional sample data":{"Treatment":"CNO_6h","RAW_FILE_NAME":"20"}
},
{
"Subject ID":"blood1_cage16",
"Sample ID":"22",
"Factors":{"Sample source":"Plasma","Genotype":"Wild-type"},
"Additional sample data":{"Treatment":"CNO_6h","RAW_FILE_NAME":"22"}
},
{
"Subject ID":"blood1_cage18",
"Sample ID":"24",
"Factors":{"Sample source":"Plasma","Genotype":"Transgenic"},
"Additional sample data":{"Treatment":"CNO_6h","RAW_FILE_NAME":"24"}
},
{
"Subject ID":"blood1_cage21",
"Sample ID":"26",
"Factors":{"Sample source":"Plasma","Genotype":"Wild-type"},
"Additional sample data":{"Treatment":"CNO_6h","RAW_FILE_NAME":"26"}
},
{
"Subject ID":"blood1_cage22",
"Sample ID":"28",
"Factors":{"Sample source":"Plasma","Genotype":"Transgenic"},
"Additional sample data":{"Treatment":"CNO_6h","RAW_FILE_NAME":"28"}
},
{
"Subject ID":"blood1_cage24",
"Sample ID":"30",
"Factors":{"Sample source":"Plasma","Genotype":"Transgenic"},
"Additional sample data":{"Treatment":"CNO_6h","RAW_FILE_NAME":"30"}
},
{
"Subject ID":"blood1_cage25",
"Sample ID":"32",
"Factors":{"Sample source":"Plasma","Genotype":"Wild-type"},
"Additional sample data":{"Treatment":"CNO_6h","RAW_FILE_NAME":"32"}
},
{
"Subject ID":"1.1inca",
"Sample ID":"34",
"Factors":{"Sample source":"Plasma","Genotype":"Wild-type"},
"Additional sample data":{"Treatment":"CNO_6h","RAW_FILE_NAME":"34"}
},
{
"Subject ID":"1.2inca",
"Sample ID":"36",
"Factors":{"Sample source":"Plasma","Genotype":"Transgenic"},
"Additional sample data":{"Treatment":"CNO_6h","RAW_FILE_NAME":"36"}
},
{
"Subject ID":"1.3inca",
"Sample ID":"38",
"Factors":{"Sample source":"Plasma","Genotype":"Wild-type"},
"Additional sample data":{"Treatment":"CNO_6h","RAW_FILE_NAME":"38"}
},
{
"Subject ID":"1.4inca",
"Sample ID":"40",
"Factors":{"Sample source":"Plasma","Genotype":"Transgenic"},
"Additional sample data":{"Treatment":"CNO_6h","RAW_FILE_NAME":"40"}
},
{
"Subject ID":"1.5inca",
"Sample ID":"42",
"Factors":{"Sample source":"Plasma","Genotype":"Transgenic"},
"Additional sample data":{"Treatment":"CNO_6h","RAW_FILE_NAME":"42"}
},
{
"Subject ID":"1.6inca",
"Sample ID":"44",
"Factors":{"Sample source":"Plasma","Genotype":"Wild-type"},
"Additional sample data":{"Treatment":"CNO_6h","RAW_FILE_NAME":"44"}
},
{
"Subject ID":"1.7inca",
"Sample ID":"46",
"Factors":{"Sample source":"Plasma","Genotype":"Transgenic"},
"Additional sample data":{"Treatment":"CNO_6h","RAW_FILE_NAME":"46"}
},
{
"Subject ID":"1.8inca",
"Sample ID":"48",
"Factors":{"Sample source":"Plasma","Genotype":"Wild-type"},
"Additional sample data":{"Treatment":"CNO_6h","RAW_FILE_NAME":"48"}
},
{
"Subject ID":"2.1inca",
"Sample ID":"50",
"Factors":{"Sample source":"Plasma","Genotype":"Wild-type"},
"Additional sample data":{"Treatment":"CNO_6h","RAW_FILE_NAME":"50"}
},
{
"Subject ID":"2.2inca",
"Sample ID":"52",
"Factors":{"Sample source":"Plasma","Genotype":"Transgenic"},
"Additional sample data":{"Treatment":"CNO_6h","RAW_FILE_NAME":"52"}
},
{
"Subject ID":"2.3inca",
"Sample ID":"54",
"Factors":{"Sample source":"Plasma","Genotype":"Transgenic"},
"Additional sample data":{"Treatment":"CNO_6h","RAW_FILE_NAME":"54"}
},
{
"Subject ID":"2.4inca",
"Sample ID":"56",
"Factors":{"Sample source":"Plasma","Genotype":"Wild-type"},
"Additional sample data":{"Treatment":"CNO_6h","RAW_FILE_NAME":"56"}
},
{
"Subject ID":"2.5inca",
"Sample ID":"58",
"Factors":{"Sample source":"Plasma","Genotype":"Transgenic"},
"Additional sample data":{"Treatment":"CNO_6h","RAW_FILE_NAME":"58"}
},
{
"Subject ID":"2.6inca",
"Sample ID":"60",
"Factors":{"Sample source":"Plasma","Genotype":"Wild-type"},
"Additional sample data":{"Treatment":"CNO_6h","RAW_FILE_NAME":"60"}
},
{
"Subject ID":"2.7inca",
"Sample ID":"62",
"Factors":{"Sample source":"Plasma","Genotype":"Transgenic"},
"Additional sample data":{"Treatment":"CNO_6h","RAW_FILE_NAME":"62"}
},
{
"Subject ID":"2.8inca",
"Sample ID":"64",
"Factors":{"Sample source":"Plasma","Genotype":"Wild-type"},
"Additional sample data":{"Treatment":"CNO_6h","RAW_FILE_NAME":"64"}
}
],
"COLLECTION":{"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_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."},

"SAMPLEPREP":{"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_TYPE":"NMR"},

"NM":{"INSTRUMENT_NAME":"Bruker Neo","INSTRUMENT_TYPE":"FT-NMR","NMR_EXPERIMENT_TYPE":"1D-1H","SPECTROMETER_FREQUENCY":"599.75 MHz"},

"NMR_METABOLITE_DATA":{
"Units":"mM",

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