Olfactory specificity regulates lipid metabolism through neuroendocrine signaling in Caenorhabditis elegans

Ayse Sena Mutlu (), Shihong Max Gao, Haining Zhang and Meng C. Wang ()
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Ayse Sena Mutlu: Huffington Center on Aging, Baylor College of Medicine
Shihong Max Gao: Graduate Program in Developmental Biology, Baylor College of Medicine
Haining Zhang: Huffington Center on Aging, Baylor College of Medicine
Meng C. Wang: Huffington Center on Aging, Baylor College of Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-15296-8

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