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Lipidomic approaches to dissect dysregulated lipid metabolism in kidney disease
Nature Reviews Nephrology ( IF 41.5 ) Pub Date : 2021-10-06 , DOI: 10.1038/s41581-021-00488-2
Judy Baek 1 , Chenchen He 2 , Farsad Afshinnia 2 , George Michailidis 3 , Subramaniam Pennathur 1, 2
Affiliation  

Dyslipidaemia is a hallmark of chronic kidney disease (CKD). The severity of dyslipidaemia not only correlates with CKD stage but is also associated with CKD-associated cardiovascular disease and mortality. Understanding how lipids are dysregulated in CKD is, however, challenging owing to the incredible diversity of lipid structures. CKD-associated dyslipidaemia occurs as a consequence of complex interactions between genetic, environmental and kidney-specific factors, which to understand, requires an appreciation of perturbations in the underlying network of genes, proteins and lipids. Modern lipidomic technologies attempt to systematically identify and quantify lipid species from biological systems. The rapid development of a variety of analytical platforms based on mass spectrometry has enabled the identification of complex lipids at great precision and depth. Insights from lipidomics studies to date suggest that the overall architecture of free fatty acid partitioning between fatty acid oxidation and complex lipid fatty acid composition is an important driver of CKD progression. Available evidence suggests that CKD progression is associated with metabolic inflexibility, reflecting a diminished capacity to utilize free fatty acids through β-oxidation, and resulting in the diversion of accumulating fatty acids to complex lipids such as triglycerides. This effect is reversed with interventions that improve kidney health, suggesting that targeting of lipid abnormalities could be beneficial in preventing CKD progression.



中文翻译:

脂质组学方法剖析肾脏疾病中脂质代谢失调

血脂异常是慢性肾脏病 (CKD) 的标志。血脂异常的严重程度不仅与 CKD 分期相关,而且与 CKD 相关的心血管疾病和死亡率相关。然而,由于脂质结构的多样性令人难以置信,因此了解脂质在 CKD 中是如何失调的具有挑战性。CKD 相关血脂异常是遗传、环境和肾脏特异性因素之间复杂相互作用的结果,要理解这些因素,需要了解基因、蛋白质和脂质的基础网络中的扰动。现代脂质组学技术试图系统地识别和量化生物系统中的脂质种类。基于质谱的各种分析平台的快速发展使得复杂脂质的鉴定变得非常精确和深入。迄今为止,脂质组学研究的见解表明,游离脂肪酸在脂肪酸氧化和复杂脂质脂肪酸组成之间分配的总体结构是 CKD 进展的重要驱动因素。现有证据表明,CKD 进展与代谢不灵活有关,反映了通过 β-氧化利用游离脂肪酸的能力下降,并导致积累的脂肪酸转移到复杂的脂质,如甘油三酯。通过改善肾脏健康的干预措施可以逆转这种影响,这表明针对脂质异常可能有利于预防 CKD 进展。迄今为止,脂质组学研究的见解表明,游离脂肪酸在脂肪酸氧化和复杂脂质脂肪酸组成之间分配的总体结构是 CKD 进展的重要驱动因素。现有证据表明,CKD 进展与代谢不灵活有关,反映了通过 β-氧化利用游离脂肪酸的能力下降,并导致积累的脂肪酸转移到复杂的脂质,如甘油三酯。通过改善肾脏健康的干预措施可以逆转这种影响,这表明针对脂质异常可能有利于预防 CKD 进展。迄今为止,脂质组学研究的见解表明,游离脂肪酸在脂肪酸氧化和复杂脂质脂肪酸组成之间分配的总体结构是 CKD 进展的重要驱动因素。现有证据表明,CKD 进展与代谢不灵活有关,反映了通过 β-氧化利用游离脂肪酸的能力下降,并导致积累的脂肪酸转移到复杂的脂质,如甘油三酯。通过改善肾脏健康的干预措施可以逆转这种影响,这表明针对脂质异常可能有利于预防 CKD 进展。

更新日期:2021-10-06
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