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A tachykinin-like neuroendocrine signalling axis couples central serotonin action and nutrient sensing with peripheral lipid metabolism
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A tachykinin-like neuroendocrine signalling axis couples central serotonin action and nutrient sensing with peripheral lipid metabolism
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Journal Article
A tachykinin-like neuroendocrine signalling axis couples central serotonin action and nutrient sensing with peripheral lipid metabolism
2017
Overview
Serotonin, a central neuromodulator with ancient ties to feeding and metabolism, is a major driver of body fat loss. However, mechanisms by which central serotonin action leads to fat loss remain unknown. Here, we report that the FLP-7 neuropeptide and its cognate receptor, NPR-22, function as the ligand-receptor pair that defines the neuroendocrine axis of serotonergic body fat loss in
Caenorhabditis elegans
. FLP-7 is secreted as a neuroendocrine peptide in proportion to fluctuations in neural serotonin circuit functions, and its release is regulated from secretory neurons via the nutrient sensor AMPK. FLP-7 acts via the NPR-22/Tachykinin2 receptor in the intestine and drives fat loss via the adipocyte triglyceride lipase ATGL-1. Importantly, this ligand-receptor pair does not alter other serotonin-dependent behaviours including food intake. For global modulators such as serotonin, the use of distinct neuroendocrine peptides for each output may be one means to achieve phenotypic selectivity.
Serotonin is a potent stimulator of fat loss and energy expenditure in several species, including
C. elegans
. Here, Palamiuc
et al
. identify the neuropeptide, FP-7, and its receptor in the intestine, NRP-22 as mediators of serotonergic body fat loss in worms.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 14/63
/ 38/77
/ 38/90
/ 631/378
/ 64/11
/ AMP-Activated Protein Kinases - metabolism
/ Animals
/ Behavior, Animal - physiology
/ Body fat
/ Caenorhabditis elegans - physiology
/ Caenorhabditis elegans Proteins - metabolism
/ Energy
/ Enzymes
/ Humanities and Social Sciences
/ Ligands
/ Lipid Metabolism - drug effects
/ Lipid Metabolism - physiology
/ Lipids
/ Mutation
/ Neurosecretory Systems - physiology
/ Peptides
/ Receptors, G-Protein-Coupled
/ Receptors, Neuropeptide - antagonists & inhibitors
/ Receptors, Neuropeptide - metabolism
/ Receptors, Neuropeptide - physiology
/ Science
