State Key Laboratory of Biocontrol, Institute of Aquatic Economic Animals, and the Guangdong Province Key Laboratory for Aquatic Economic Animals, School of Life Sciences, Sun Yat-Sen University, Guangzhou, 510275, China.
Zhanjiang City State Key Laboratory of Marine Ecology and Environment, Fisheries College,Guangdong Ocean University, Zhanjiang, 524088, China.
Sci Rep. 2017 Nov 7;7(1):14643. doi: 10.1038/s41598-017-15138-6.
Spexin1 (SPX1) is a newly discovered neuropeptide in vertebrates. Its biological function remains to be elucidated. In this study, we have generated the zebrafish spx1 mutant lines using transcription activator-like effector nucleases. Phenotypes of the spx1 mutant zebrafish were analyzed in order to understand the effects on reproduction and food intake. The reproductive capability is not impaired in spx1 mutant zebrafish. However, we found that the spx1 mutant fish had a higher food intake than the wild type (WT) fish. Real-time PCR revealed that the expression level of agouti-relate protein 1 (AgRP1), a significant appetite stimulant, was significantly higher in spx1 mutant fish after feeding. Intracranial administration of SPX1 could also reduce the mRNA expression of the AgRP1. These data suggest that SPX1 might decrease the food intake by down regulating the expression level of agrp1. Furthermore, spx1 mutant fish exhibited higher glucose, triacylglycerol and cholesterol in the serum than WT fish. However, the hyperphagia did not lead to a higher growth rate or body fat percentage. Taken together, our study suggests that SPX1 may serve as a satiety signal molecular by suppressing the AgRP1 in the brain.
Spexin1 (SPX1) 是脊椎动物中新发现的一种神经肽。其生物学功能尚待阐明。在这项研究中，我们使用转录激活因子样效应物核酸酶生成了斑马鱼 spx1 突变体系。分析了 spx1 突变体斑马鱼的表型，以了解其对生殖和食物摄入的影响。spx1 突变体斑马鱼的生殖能力没有受损。然而，我们发现 spx1 突变鱼的食物摄入量高于野生型（WT）鱼。实时 PCR 显示，喂食后 spx1 突变鱼中食欲刺激物 agouti 相关蛋白 1 (AgRP1) 的表达水平显著升高。颅内给予 SPX1 也可以降低 AgRP1 的 mRNA 表达。这些数据表明 SPX1 可能通过下调 agrp1 的表达水平来减少食物摄入。此外，spx1 突变鱼的血清中葡萄糖、三酰甘油和胆固醇水平高于 WT 鱼。然而，过度摄食并没有导致更高的生长速度或体脂百分比。总之，我们的研究表明，SPX1 可能通过抑制脑中的 AgRP1 作为一种饱腹感信号分子。
