title: A tachykinin-like neuroendocrine signalling axis couples central serotonin action and nutrient sensing with peripheral lipid metabolism.
abstract: 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.
authors.affiliation: Department of Chemical Physiology and The Dorris Neuroscience Center, 1 Barnard Drive, Oceanside, California 92056, USA.|The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California, USA.
authors.forename: Lavinia
authors.initials: L
authors.lastname: Palamiuc
authors.affiliation: Mira Costa College, 1 Barnard Drive, Oceanside, California 92056, USA.
authors.forename: Tallie
authors.initials: T
authors.lastname: Noble
authors.affiliation: The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Witham
authors.affiliation: The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California, USA.
authors.forename: Harkaranveer
authors.initials: H
authors.lastname: Ratanpal
authors.affiliation: The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California, USA.|Kellogg School of Science and Technology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California, USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Vaughan
authors.affiliation: Department of Chemical Physiology and The Dorris Neuroscience Center, 1 Barnard Drive, Oceanside, California 92056, USA.|The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California, USA.
authors.forename: Supriya
authors.initials: S
authors.lastname: Srinivasan
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000273:Adipose Tissue / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D004435:Eating / Q000502:physiology; D007211:Indoles / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology; D009154:Mutation; D009474:Neurons / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism / Q000502:physiology*; D009490:Neurosecretory Systems / Q000502:physiology; D010880:Piperidines / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D029742:Caenorhabditis elegans Proteins; C000629205:FLP-7 protein, C elegans; C092990:GR 159897; D007211:Indoles; C512610:NPR-22 protein, C elegans; D009479:Neuropeptides; D010880:Piperidines; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D012701:Serotonin; D055372:AMP-Activated Protein Kinases