Kwon Saebom, Park Kyu-Sang, Yoon Kyoung-Hye
Department of Physiology, Yonsei University Wonju College of Medicine, Wonju 26426, Republic of Korea.
Mitohormesis Research Center, Yonsei University Wonju College of Medicine, Wonju 26426, Republic of Korea.
Life (Basel). 2023 Dec 15;13(12):2346. doi: 10.3390/life13122346.
Although the importance of lipid homeostasis in neuronal function is undisputed, how they are regulated within neurons to support their unique function is an area of active study. NHR-49 is a nuclear hormone receptor functionally similar to PPARα, and a major lipid regulator in . Although expressed in most tissues, little is known about its roles outside the intestine, the main metabolic organ of . Here, using tissue- and neuron-type-specific transgenic strains, we examined the contribution of neuronal NHR-49 to cell-autonomous and non-autonomous mutant phenotypes. We examined lifespan, brood size, early egg-laying, and reduced locomotion on food. We found that lifespan and brood size could be rescued by neuronal NHR-49, and that NHR-49 in cholinergic and serotonergic neurons is sufficient to restore lifespan. For behavioral phenotypes, NHR-49 in serotonergic neurons was sufficient to control egg-laying, whereas no single tissue or neuron type was able to rescue the enhanced on-food slowing behavior. Our study shows that NHR-49 can function in single neuron types to regulate physiology and behavior, and provides a platform to further investigate how lipid metabolism in neurons impact neuronal function and overall health of the organism.
尽管脂质稳态在神经元功能中的重要性毋庸置疑，但它们如何在神经元内受到调节以支持其独特功能仍是一个活跃的研究领域。NHR-49是一种与PPARα功能相似的核激素受体，是[具体生物]中的主要脂质调节因子。尽管在大多数组织中都有表达，但关于它在肠道（[具体生物]的主要代谢器官）之外的作用却知之甚少。在这里，我们使用组织和神经元类型特异性转基因菌株，研究了神经元NHR-49对细胞自主和非自主[具体突变体]表型的贡献。我们检测了寿命、产卵量、早期产卵情况以及在食物上运动能力的下降。我们发现神经元NHR-49可以挽救寿命和产卵量，并且胆碱能和5-羟色胺能神经元中的NHR-49足以恢复寿命。对于行为表型，5-羟色胺能神经元中的NHR-49足以控制产卵，而没有单一的组织或神经元类型能够挽救食物上增强的运动迟缓行为。我们的研究表明，NHR-49可以在单一神经元类型中发挥作用，调节[具体生物]的生理和行为，并为进一步研究神经元中的脂质代谢如何影响神经元功能和生物体的整体健康提供了一个平台。
