title: An integrated serotonin and octopamine neuronal circuit directs the release of an endocrine signal to control C. elegans body fat.
abstract: Serotonin (5-hydroxytryptamine, 5-HT) is an ancient and conserved neuromodulator of energy balance. Despite its importance, the neural circuits and molecular mechanisms underlying 5-HT-mediated control of body fat remain poorly understood. Here, we decipher the serotonergic neural circuit for body fat loss in C. elegans and show that the effects of 5-HT require signaling from octopamine, the invertebrate analog of adrenaline, to sustain body fat loss. Our results provide a potential molecular explanation for the long-observed potent effects of combined serotonergic and adrenergic weight loss drugs. In metabolic tissues, we find that the conserved regulatory adipocyte triglyceride lipase ATGL-1 drives serotonergic fat loss. We show that the serotonergic chloride channel MOD-1 relays a long-range endocrine signal from C. elegans body cavity neurons to control distal ATGL-1 function, via the nuclear receptor NHR-76. Our findings establish a conserved neuroendocrine axis operated by neural serotonergic and adrenergic-like signaling to regulate body fat.
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Tallie
authors.initials: T
authors.lastname: Noble
authors.forename: Jonathan
authors.initials: J
authors.lastname: Stieglitz
authors.forename: Supriya
authors.initials: S
authors.lastname: Srinivasan
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D018118:Chloride Channels / Q000378:metabolism; D004703:Endocrine System / Q000378:metabolism*; D008066:Lipolysis; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism*; D009655:Octopamine / Q000378:metabolism*; D009832:Olfactory Nerve / Q000166:cytology / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D029742:Caenorhabditis elegans Proteins; D018118:Chloride Channels; D009655:Octopamine; D012701:Serotonin