Spexin Suppress Food Intake in Zebrafish: Evidence from Gene Knockout Study.

Spexin Suppress Food Intake in Zebrafish: Evidence from Gene Knockout Study.
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Spexin 抑制斑马鱼的食物摄入:基因敲除研究的证据

DOI:
10.1038/s41598-017-15138-6
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发表时间:
2017-11-07
期刊:
影响因子:
4.6
通讯作者:
Cheng CHK
Cheng CHK
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zheng B;Li S;Liu Y;Li Y;Chen H;Tang H;Liu X;Lin H;Zhang Y;Cheng CHK

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Spexin 1(SPX 1)是一种新发现的脊椎动物神经肽。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核酸酶产生了斑马鱼spx 1 −/−突变株系。分析了spx 1 −/−突变斑马鱼的表型,以了解其对繁殖和食物摄入的影响。spx 1突变斑马鱼的繁殖能力没有受到损害。然而,我们发现spx 1 −/−突变鱼的食物摄入量高于野生型(WT)鱼。实时PCR显示,在spx 1 −/−突变的鱼中,摄食后的Agouti-related protein 1(AgRP 1)表达水平显着升高,AgRP 1是一种显着的食欲刺激剂。颅内注射SPX 1也可降低AgRP 1的mRNA表达。这些数据表明,SPX 1可能通过下调agrp 1的表达水平来减少摄食量。此外,spx 1 −/−突变鱼的血清中葡萄糖、三酰甘油和胆固醇含量高于野生型鱼。然而,摄食过多并没有导致更高的生长速度或体脂百分比。综上所述,我们的研究表明,SPX 1可能通过抑制大脑中的AgRP 1而作为饱腹感信号分子。
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.
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