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Activation of GFRAL...
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Engström-Ruud, LindaGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
(author)
Activation of GFRAL+ neurons induces hypothermia and glucoregulatory responses associated with nausea and torpor.
- Article/chapterEnglish2024
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Numbers
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LIBRIS-ID:oai:gup.ub.gu.se/338569
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https://gup.ub.gu.se/publication/338569URI
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https://doi.org/10.1016/j.celrep.2024.113960DOI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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GFRAL-expressing neurons actuate aversion and nausea, are targets for obesity treatment, and may mediate metformin effects by long-term GDF15-GFRAL agonism. Whether 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 indicate 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.
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Font Gironès, FerranGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology(Swepub:gu)xfontf
(author)
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Zajdel, Joanna
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Kern, Lara
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Teixidor-Deulofeu, Júlia
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Mannerås Holm, Louise,1980Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberg Laboratory,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xmanlo
(author)
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Carreras, AlbaGothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory(Swepub:gu)xcaalb
(author)
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Becattini, BarbaraGothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory(Swepub:gu)xbecba
(author)
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Björefeldt, Andreas,1982Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology(Swepub:gu)xbjoaw
(author)
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Hanse, Eric,1962Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology(Swepub:gu)xhaeri
(author)
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Fenselau, Henning
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Solinas, GiovanniGothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory(Swepub:gu)xsolgi
(author)
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Brüning, Jens C
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Wunderlich, Thomas F
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Bäckhed, Fredrik,1973Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberg Laboratory,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xbafre
(author)
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Ruud, Johan,1978Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology(Swepub:gu)xruujo
(author)
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Göteborgs universitetInstitutionen för neurovetenskap och fysiologi, sektionen för fysiologi
(creator_code:org_t)
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In:Cell reports43:42211-1247
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Zajdel, Joanna
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