PDF(Pubmed)
Abstract：
A detailed knowledge of the lipid composition of components of nephrons is crucial for understanding physiological processes and the development of kidney diseases. However, the lipidomic composition of kidney tubular segments is unknown. We manually isolated the proximal convoluted tubule (PCT), the cortical thick ascending limb of Henle\'s loop, and the cortical collecting duct from 5 lean and obese mice and subjected the samples to shotgun lipidomics analysis by high-resolution mass spectrometry acquisition. Across all samples, more than 500 lipid species were identified, quantified, and compared. We observed significant compositional differences among the 3 tubular segments, which serve as true signatures. These intrinsic lipidomic features are associated with a distinct proteomic program that regulates highly specific physiological functions. The distinctive lipidomic features of each of the 3 segments are mostly based on the relative composition of neutral lipids, long-chain polyunsaturated fatty acids, sphingolipids, and ether phospholipids. These features support the hypothesis of a lipotype assigned to specific tubular segments. Obesity profoundly impacts the lipotype of PCT. In conclusion, we present a comprehensive lipidomic analysis of 3 cortical segments of mouse kidney tubules. This valuable resource provides unparalleled detail that enhances our understanding of tubular physiology and the potential impact of pathological conditions.
摘要：
详细了解肾单位成分的脂质组成对于理解生理过程和肾脏疾病的发展至关重要。然而,肾小管段的脂质组成未知.我们手动分离了近曲小管(PCT)，来自五只瘦肥胖小鼠的Henle'sloop（cTAL）和皮质收集管（CCD）的皮质厚上升肢体，并通过高分辨率质谱采集对样品进行shot弹枪脂质组学分析。在所有样品中，超过五百种脂质被鉴定出来,量化和比较。我们观察到三个管状段之间的显着组成差异，作为真正的签名。这些固有的脂质组学特征与调节高度特异性生理功能的独特蛋白质组学程序相关。三个部分中每一个的独特脂质组学特征主要基于中性脂质的相对组成，长链多不饱和脂肪酸，鞘脂，和醚磷脂。这些特征支持指定给特定管状节段的脂型假说。肥胖深刻影响近端曲小管的脂型。总之,我们对小鼠肾小管的三个皮质段进行了全面的脂质组学分析。这一宝贵的资源提供了无与伦比的细节，增强了我们对管状生理学和病理状况潜在影响的理解。
