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CRISPR/Cas9 诱导的 LEAP2 和 GHSR1a 敲除突变斑马鱼表现出异常生长和脂质代谢受损。

CRISPR/Cas9-induced LEAP2 and GHSR1a knockout mutant zebrafish displayed abnormal growth and impaired lipid metabolism.

机构信息

Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai, China; International Research Center for Marine Biosciences, Ministry of Science and Technology, Shanghai Ocean University, Shanghai, China.

Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai, China; International Research Center for Marine Biosciences, Ministry of Science and Technology, Shanghai Ocean University, Shanghai, China.

出版信息

Gen Comp Endocrinol. 2024 Sep 1;355:114563. doi: 10.1016/j.ygcen.2024.114563. Epub 2024 Jun 1.

DOI:10.1016/j.ygcen.2024.114563
PMID:38830459
Abstract

Investigating the principles of fish fat deposition and conducting related research are current focal points in fish nutrition. This study explores the endocrine regulation of LEAP2 and GHSR1a in zebrafish by constructing mutantmodels andexamining the effects of the endocrine factors LEAP2 and its receptor GHSR1a on zebrafish growth, feeding, and liver fat deposition. Compared to the wild type (WT), the mutation of LEAP2 results in increased feeding and decreased swimming in zebrafish. The impact is more pronounced in adult female zebrafish, characterized by increased weight, length, width, and accumulation of lipid droplets in the liver.Incontrast, deficiency in GHSR1a significantly reduces the growth of male zebrafish and markedly decreases liver fat deposition.These research findings indicate the crucial roles of LEAP2 and GHSR1a in zebrafish feeding, growth, and intracellular fat metabolism. This study, for the first time, investigated the endocrine metabolic regulation functions of LEAP2 and GHSR1a in the model organism zebrafish, providing initial insights into their effects and potential mechanisms on zebrafish fat metabolism.

摘要

研究鱼类脂肪沉积的原理并开展相关研究是当前鱼类营养学的重点。本研究通过构建突变模型,探讨了 LEAP2 和 GHSR1a 在内分泌调节中的作用,研究了内分泌因子 LEAP2 及其受体 GHSR1a 对斑马鱼生长、摄食和肝脏脂肪沉积的影响。与野生型(WT)相比,LEAP2 的突变导致斑马鱼摄食增加,游泳减少。这种影响在成年雌性斑马鱼中更为明显,表现为体重、体长、体宽增加,肝脏中脂质滴积累增多。相比之下,GHSR1a 的缺乏显著降低了雄性斑马鱼的生长速度,并显著减少了肝脏脂肪沉积。这些研究结果表明,LEAP2 和 GHSR1a 在斑马鱼摄食、生长和细胞内脂肪代谢中起关键作用。本研究首次研究了 LEAP2 和 GHSR1a 在模式生物斑马鱼中的内分泌代谢调节功能,初步探讨了它们对斑马鱼脂肪代谢的影响及其潜在机制。

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