FAM237衍生的小蛋白在能量稳态中的作用：脊椎动物神经分泌蛋白GL和GM的比较视角

摘要(中文译文)

下丘脑神经肽和神经环路整合外周信号、营养需求及环境线索，从而协调脊椎动物的能量稳态。神经分泌蛋白GL（NPGL）和神经分泌蛋白GM（NPGM）是由FAM237家族旁系同源基因编码的下丘脑小分泌蛋白。这些基因最初在鸟类中被鉴定，但数据库检索显示其在脊椎动物中具有进化保守性，提示NPGL和NPGM具有保守的生理作用。既往关于NPGL的研究已证实，NPGL在哺乳动物和鸟类中均以依赖饮食和品系的方式促进过度进食和脂肪蓄积。越来越多的证据表明，NPGM也可能参与摄食过多和肥胖。值得注意的是，转录组学和组织学分析的最新进展揭示了Npgl和Npgm在参与能量稳态的特定下丘脑神经元亚群中的表达。本文中，我们总结了理解NPGL和NPGM代谢作用的最新进展。随后，我们聚焦于表达Npgl和Npgm的神经元的细胞身份。最后，我们讨论了未来研究方向以及NPGL和NPGM调控代谢的潜在分子机制。研究调控能量代谢的NPGL/NPGM系统，将有助于理解脊椎动物能量稳态的保守机制和物种特异性机制。

Abstract

Hypothalamic neuropeptides and neural circuits integrate peripheral signals, nutrient demand, and environmental cues to orchestrate energy homeostasis in vertebrates. Neurosecretory protein GL (NPGL) and neurosecretory protein GM (NPGM) are hypothalamic small secretory proteins encoded by paralogous genes of the FAM237 family. These genes were initially identified in birds, but database search showed evolutionary conservation across vertebrates, suggesting conserved physiological roles for NPGL and NPGM. Previous studies on NPGL have demonstrated that NPGL stimulates overeating and fat accumulation in a diet- and strain-dependent manner in both mammals and birds. Accumulating evidence suggests that NPGM may also be involved in hyperphagia and adiposity. Notably, recent progress in transcriptomics and histological analyses has revealed expression of Npgl and Npgm in specific hypothalamic neuronal subpopulations involved in energy homeostasis. Here, we summarize recent progress in understanding the metabolic actions of NPGL and NPGM. We then focus on the cellular identity of Npgl- and Npgm-expressing neurons. Finally, we discuss future directions and potential molecular mechanisms of metabolic regulation by NPGL and NPGM. Investigating the NPGL/NPGM system, which regulates energy metabolism, will contribute to understanding both conserved and species-specific mechanisms of energy homeostasis across vertebrates.

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