Publication

Dietary L-Glu sensing by enteroendocrine cells adjusts food intake via modulating gut PYY/NPF secretion

Résumé

Amino acid availability is monitored by animals to adapt to their nutritional environment. Beyond gustatory receptors and systemic amino acid sensors, enteroendocrine cells (EECs) are believed to directly percept dietary amino acids and secrete regulatory peptides. However, the cellular machinery underlying amino acid-sensing by EECs and how EEC-derived hormones modulate feeding behavior remain elusive. Here, by developing tools to specifically manipulate EECs, we find that Drosophila neuropeptide F (NPF) from mated female EECs inhibits feeding, similar to human PYY. Mechanistically, dietary L-Glutamate acts through the metabotropic glutamate receptor mGluR to decelerate calcium oscillations in EECs, thereby causing reduced NPF secretion via dense-core vesicles. Furthermore, two dopaminergic enteric neurons expressing NPFR perceive EEC-derived NPF and relay an anorexigenic signal to the brain. Thus, our findings provide mechanistic insights into how EECs assess food quality and identify a conserved mode of action that explains how gut NPF/PYY modulates food intake.|Enteroendocrine cells in the gut sense food to regulate feeding behavior. Here, the authors show in Drosophila L-glutamate reduces the frequency of calcium oscillations in enteroendocrine cells and decreases the release of NPF, thereby reducing the activation of a pair of anorexic enteric neurons.

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Concepts associés (33)
Acide glutamique
L'acide glutamique (abréviations IUPAC-IUBMB : Glu et E), ou glutamate sous la forme anionique de l'acide glutamique, est un acide dont l'énantiomère L est l'un des aminés protéinogènes, encodé sur les ARN messagers par les codons GAA et GAG. Il est caractérisé par la présence d'un groupe carboxyle –COOH à l'extrémité de sa chaîne latérale, ce qui en fait un résidu acide chargé négativement dans les protéines. Son rayon de van der Waals vaut .
Glutamate receptor
Glutamate receptors are synaptic and non synaptic receptors located primarily on the membranes of neuronal and glial cells. Glutamate (the conjugate base of glutamic acid) is abundant in the human body, but particularly in the nervous system and especially prominent in the human brain where it is the body's most prominent neurotransmitter, the brain's main excitatory neurotransmitter, and also the precursor for GABA, the brain's main inhibitory neurotransmitter.
Neuropeptide
Un neuropeptide est un type d'hormone, plus précisément un peptide sécrété par un neurone et ayant essentiellement une fonction de neuromodulateur. Ce sont des polypeptides ou de petites protéines formés de quelques acides aminés jusqu'à plusieurs centaines (191 pour l'hormone de croissance). Ils se lient généralement à un récepteur couplé à une protéine G capable, lorsqu'elle est activée, de déclencher une chaîne de réactions mettant en œuvre plusieurs effecteurs pouvant moduler finement la transmission du message.
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