Gut-brain communication by distinct sensory neurons differently controls feeding and glucose metabolism

Borgmann Diba; Ciglieri Elisa; Biglari NasimBrandt ClausCremer Anna LenaBackes HeikoTittgemeyer MarcWunderlich F. ThomasBruning Jens C.Fenselau Henning

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Gut-brain communication by distinct sensory neurons differently controls feeding and glucose metabolism

机译：Gut-brain communication by distinct sensory neurons differently controls feeding and glucose metabolism

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Sensory neurons relay gut-derived signals to the brain, yet the molecular and functional organization of distinct populations remains unclear. Here, we employed intersectional genetic manipulations to probe the feeding and glucoregulatory function of distinct sensory neurons. We reconstruct the gut innervation patterns of numerous molecularly defined vagal and spinal afferents and identify their downstream brain targets. Bidirectional chemogenetic manipulations, coupled with behavioral and circuit mapping analysis, demonstrated that gut-innervating, glucagon-like peptide 1 receptor (GLP1R)-expressing vagal afferents relay anorexigenic signals to parabrachial nucleus neurons that control meal termination. Moreover, GLP1R vagal afferent activation improves glucose tolerance, and their inhibition elevates blood glucose levels independent of food intake. In contrast, gut-innervating, GPR65-expressing vagal afferent stimulation increases hepatic glucose production and activates parabrachial neurons that control normoglycemia, but they are dispensable for feeding regulation. Thus, distinct gut-innervating sensory neurons differentially control feeding and glucoregulatory neurocircuits and may provide specific targets for metabolic control.

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《Cell metabolism》 |2021年第7期|1466-1482|共25页
作者
Borgmann Diba; Ciglieri Elisa; Biglari NasimBrandt ClausCremer Anna LenaBackes HeikoTittgemeyer MarcWunderlich F. ThomasBruning Jens C.Fenselau Henning;
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Max Planck Inst Metab Res, Synapt Transmiss Energy Homeostasis Grp, Gleueler Str 50, D-50931;

Max Planck Inst Metab Res, Dept Neuronal Control Metab, Gleueler Str 50, D-50931 Cologne, Germany;

Max Planck Inst Metab Res, Translat Neurocircuitry Grp, Gleueler Str 50, D-50931 Cologne, GermanyUniv Hosp Cologne, Ctr Endocrinol Diabet & Prevent Med CEDP, Kerpener Str 26, D-50937 Cologne;

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中图分类内分泌腺疾病及代谢病;
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Gut-brain communication by distinct sensory neurons differently controls feeding and glucose metabolism

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