肾皮质小管部分的脂质组图谱鉴定出具有生理意义的脂型

Function Pub Date : 2024-03-30 DOI:10.1093/function/zqae016
L. Cheval, Virginie Poindessous, Julio L Sampaio, Gilles Crambert, Nicolas Pallet
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摘要

详细了解肾小管成分的脂质组成对于了解生理过程和肾脏疾病的发展至关重要。然而,肾小管各节段的脂质组成尚不清楚。我们人工分离了五只瘦小鼠和肥胖小鼠的近曲小管(PCT)、Henle's襻皮质粗升支(cTAL)和皮质集合管(CCD),并通过高分辨质谱采集对样本进行了枪式脂质组学分析。对所有样本中的五百多种脂质进行了鉴定、量化和比较。我们观察到三个管段之间存在明显的成分差异,这就是真正的特征。这些固有的脂质体特征与调节高度特异性生理功能的独特蛋白质组程序有关。三个节段各自不同的脂质体特征主要基于中性脂质、长链多不饱和脂肪酸、鞘脂和醚磷脂的相对组成。这些特征支持为特定管段分配脂型的假设。肥胖对近曲小管的脂质型有深远影响。总之,我们对小鼠肾小管的三个皮质区段进行了全面的脂质体分析。这一宝贵的资源提供了无与伦比的细节,加深了我们对肾小管生理学和病理条件潜在影响的理解。
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Lipidomic Profiling of Kidney Cortical Tubule Segments Identifies Lipotypes with Physiological Implications
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 (cTAL) and the cortical collecting duct (CCD) from five lean and obese mice and subjected the samples to shotgun lipidomics analysis by high resolution mass spectrometry acquisition. Across all samples, more than five hundred lipid species were identified, quantified and compared. We observed significant compositional differences among the three 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 three 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 proximal convoluted tubules. In conclusion, we present a comprehensive lipidomic analysis of three 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.
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