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Cell Metab. 2013 Nov 5;18(5):672-84. doi: 10.1016/j.cmet.2013.09.007. Epub 2013 Oct 10.

An integrated serotonin and octopamine neuronal circuit directs the release of an endocrine signal to control C. elegans body fat.

Author information

1
Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

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.

PMID:
24120942
PMCID:
PMC3882029
DOI:
10.1016/j.cmet.2013.09.007
[Indexed for MEDLINE]
Free PMC Article

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