RRC ID 46114
Author Noble T, Stieglitz J, Srinivasan S.
Title An integrated serotonin and octopamine neuronal circuit directs the release of an endocrine signal to control C. elegans body fat.
Journal Cell Metab
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.
Volume 18(5)
Pages 672-84
Published 2013-11-5
DOI 10.1016/j.cmet.2013.09.007
PII S1550-4131(13)00376-8
PMID 24120942
PMC PMC3882029
MeSH Adipose Tissue / metabolism* Animals Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Chloride Channels / metabolism Endocrine System / metabolism* Lipolysis Models, Biological Neurons / metabolism* Octopamine / metabolism* Olfactory Nerve / cytology Olfactory Nerve / metabolism Serotonin / metabolism* Signal Transduction* Transcription, Genetic / drug effects
IF 21.567
Times Cited 44
C.elegans tm2146 tm1846