Olfactory specificity regulates lipid metabolism through neuroendocrine signaling in Caenorhabditis elegans
Open Access
- 19 March 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 11 (1), 1-15
- https://doi.org/10.1038/s41467-020-15296-8
Abstract
Olfactory and metabolic dysfunctions are intertwined phenomena associated with obesity and neurodegenerative diseases; yet how mechanistically olfaction regulates metabolic homeostasis remains unclear. Specificity of olfactory perception integrates diverse environmental odors and olfactory neurons expressing different receptors. Here, we report that specific but not all olfactory neurons actively regulate fat metabolism without affecting eating behaviors in Caenorhabditis elegans, and identified specific odors that reduce fat mobilization via inhibiting these neurons. Optogenetic activation or inhibition of the responsible olfactory neural circuit promotes the loss or gain of fat storage, respectively. Furthermore, we discovered that FLP-1 neuropeptide released from this olfactory neural circuit signals through peripheral NPR-4/neuropeptide receptor, SGK-1/serum- and glucocorticoid-inducible kinase, and specific isoforms of DAF-16/FOXO transcription factor to regulate fat storage. Our work reveals molecular mechanisms underlying olfactory regulation of fat metabolism, and suggests the association between olfactory perception specificity of each individual and his/her susceptibility to the development of obesity.Funding Information
- U.S. Department of Health & Human Services | NIH | Office of Extramural Research, National Institutes of Health (R01AG062257, DP1DK113644)
- U.S. Department of Health & Human Services | NIH | Office of Extramural Research, National Institutes of Health
- March of Dimes Foundation
- Welch Foundation
- Howard Hughes Medical Institute
This publication has 76 references indexed in Scilit:
- Effects ofCaenorhabditis elegans sgk‐1mutations on lifespan, stress resistance, andDAF‐16/FoxOregulationAging Cell, 2013
- The homeodomain protein hmbx-1 maintains asymmetric gene expression in adult C. elegans olfactory neuronsGenes & Development, 2010
- A new DAF-16 isoform regulates longevityNature, 2010
- Olfactory Perception: Receptors, Cells, and CircuitsCell, 2009
- Neural and Molecular Dissection of a C. elegans Sensory Circuit that Regulates Fat and FeedingCell Metabolism, 2008
- An AMPK-FOXO Pathway Mediates Longevity Induced by a Novel Method of Dietary Restriction in C. elegansCurrent Biology, 2007
- Expression and regulation of an FMRFamide‐related neuropeptide gene family in Caenorhabditis elegansJournal of Comparative Neurology, 2004
- Regulation of Body Size and Behavioral State of C. elegans by Sensory Perception and the EGL-4 cGMP-Dependent Protein KinaseNeuron, 2002
- Food and metabolic signalling defects in a Caenorhabditis elegans serotonin-synthesis mutantNature, 2000
- Effects of starvation and neuroactive drugs on feeding in Caenorhabditis elegansJournal of Experimental Zoology, 1990