Huffington Center on Aging, Baylor College of Medicine, Houston, TX, 77030, USA.
Graduate Program in Developmental Biology, Baylor College of Medicine, Houston, TX, 77030, USA.
Nat Commun. 2020 Mar 19;11(1):1450. doi: 10.1038/s41467-020-15296-8.
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.
嗅觉和代谢功能障碍是与肥胖和神经退行性疾病相关的交织现象；然而，嗅觉如何调节代谢稳态的机制尚不清楚。嗅觉感知的特异性整合了不同的环境气味和表达不同受体的嗅觉神经元。在这里，我们报告说，特定但不是所有的嗅觉神经元在不影响秀丽隐杆线虫摄食行为的情况下主动调节脂肪代谢，并确定了通过抑制这些神经元减少脂肪动员的特定气味。负责的嗅觉神经回路的光遗传学激活或抑制分别促进脂肪储存的损失或获得。此外，我们发现从这个嗅觉神经回路中释放的 FLP-1 神经肽通过外周 NPR-4/神经肽受体、SGK-1/血清和糖皮质激素诱导的激酶以及特定的 DAF-16/FOXO 转录因子同工型信号传导来调节脂肪储存。我们的工作揭示了嗅觉调节脂肪代谢的分子机制，并提示了每个人的嗅觉感知特异性与其易患肥胖发展的相关性。
