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Metabolomic and transcriptomic profiling of adult mice and larval zebrafish leptin mutants reveal a common pattern of changes in metabolites and signaling pathways
Cell and Bioscience ( IF 7.5 ) Pub Date : 2021-07-07 , DOI: 10.1186/s13578-021-00642-0
Yi Ding 1 , Mariëlle C Haks 2 , Gabriel Forn-Cuní 1 , Junling He 1 , Natalia Nowik 1, 3 , Amy C Harms 4 , Thomas Hankemeier 4 , Muhamed N H Eeza 5, 6 , Jörg Matysik 6 , A Alia 5, 7 , Herman P Spaink 1
Affiliation  

Leptin plays a critical role in the regulation of metabolic homeostasis. However, the molecular mechanism and cross talks between leptin and metabolic pathways leading to metabolic homeostasis across different species are not clear. This study aims to explore the effects of leptin in mice and zebrafish larvae by integration of metabolomics and transcriptomics. Different metabolomic approaches including mass spectrometry, nuclear magnetic resonance (NMR) and high-resolution magic-angle-spinning NMR spectrometry were used to investigate the metabolic changes caused by leptin deficiency in mutant ob/ob adult mice and lepb−/− zebrafish larvae. For transcriptome studies, deep RNA sequencing was used. Thirteen metabolites were identified as common biomarkers discriminating ob/ob mice and lepb−/− zebrafish larvae from their respective wild type controls: alanine, citrulline, ethanolamine, glutamine, glycine, histidine, isoleucine, leucine, methionine, phenylalanine, putrescine, serine and threonine. Moreover, we also observed that glucose and lipid levels were increased in lepb−/− zebrafish larvae compared to the lepb+/+ group. Deep sequencing showed that many genes involved in proteolysis and arachidonic acid metabolism were dysregulated in ob/ob mice heads and lepb mutant zebrafish larvae compared to their wild type controls, respectively. Leptin deficiency leads to highly similar metabolic alterations in metabolites in both mice and zebrafish larvae. These metabolic changes show similar features as observed during progression of tuberculosis in human patients, mice and zebrafish larvae. In addition, by studying the transcriptome, we found similar changes in gene regulation related to proteolysis and arachidonic acid metabolism in these two different in vivo models.

中文翻译:

成年小鼠和幼虫斑马鱼瘦素突变体的代谢组学和转录组学分析揭示了代谢物和信号通路变化的共同模式

瘦素在调节代谢稳态中起关键作用。然而,导致不同物种代谢稳态的瘦素和代谢途径之间的分子机制和相互影响尚不清楚。本研究旨在通过代谢组学和转录组学的整合探索瘦素对小鼠和斑马鱼幼虫的影响。包括质谱、核磁共振 (NMR) 和高分辨率魔角旋转 NMR 光谱在内的不同代谢组学方法用于研究突变体 ob/ob 成年小鼠和 lepb-/- 斑马鱼幼虫瘦素缺乏引起的代谢变化。对于转录组研究,使用了深度 RNA 测序。13 种代谢物被鉴定为常见的生物标志物,可将 ob/ob 小鼠和 lepb-/- 斑马鱼幼虫与它们各自的野生型对照区分开来:丙氨酸、瓜氨酸、乙醇胺、谷氨酰胺、甘氨酸、组氨酸、异亮氨酸、亮氨酸、甲硫氨酸、苯丙氨酸、腐胺、丝氨酸和苏氨酸。此外,我们还观察到,与 lepb+/+ 组相比,lepb-/- 斑马鱼幼虫的葡萄糖和脂质水平增加。深度测序显示,与野生型对照相比,在 ob/ob 小鼠头部和 lepb 突变斑马鱼幼虫中,许多参与蛋白水解和花生四烯酸代谢的基因分别失调。瘦素缺乏导致小鼠和斑马鱼幼虫的代谢物发生高度相似的代谢改变。这些代谢变化显示出与人类患者、小鼠和斑马鱼幼虫结核病进展过程中观察到的相似特征。此外,通过研究转录组,
更新日期:2021-07-08
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