Área de Bioquímica y Biología Molecular, Departamento de Ciencias Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Alcorcón, Madrid, Spain.
Área de Bioquímica y Biología Molecular, Departamento de Ciencias Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Alcorcón, Madrid, Spain,
Nephron. 2019;143(1):28-32. doi: 10.1159/000494694. Epub 2019 Jan 9.
The recent and ongoing worldwide increase in the prevalence of obesity parallels the increase in the incidence of chronic kidney disease (CKD). This association suggests an implication of lipotoxicity in the development of kidney diseases. The increased influx of lipids into the kidney can be explained in the context of the "Adipose Tissue Expandability Hypothesis". This hypothesis states that the adipose tissue has a limited expansion capability, which is different for each individual, and once this limit is reached, the adipose tissue cannot store any more lipids and will thus release them into the bloodstream. The accumulation of lipids in the kidney is known as renal lipotoxicity. Renal lipotoxicity is known to cause detrimental effects on the kidney by several mechanisms of action including reclusion of pro-inflammatory factors, oxidative and ER stress development, insulin resistance (IR), lipid metabolism deregulation or renin-angiotensin aldosterone system overactivation. Isoform peroxisome proliferator-activated receptor gamma (PPARγ) seems to play an important role in the development of this lipotoxicity as proven by several studies in -animals and cultured cells. Thus, PPARγ agonists are of -interest in the therapeutic approach to treat CKD in the context of obesity. This review aims to summarize our current knowledge of the mechanism by which lipotoxicity affects renal structure and function using in vivo and in vitro models as examples focusing on PPARγ.
近年来，全球肥胖患病率的上升与慢性肾脏病（CKD）发病率的上升并行不悖。这种相关性表明脂毒性在肾脏疾病的发展中具有一定的作用。肾脏中脂质的大量涌入可以用“脂肪组织可扩展性假说”来解释。该假说指出，脂肪组织的扩张能力是有限的，而且每个人的能力都不同，一旦达到这个极限，脂肪组织就无法再储存更多的脂肪，因此会将其释放到血液中。脂质在肾脏中的积累被称为肾脂毒性。肾脂毒性通过多种作用机制对肾脏造成有害影响，包括炎症因子的隔离、氧化和内质网应激的发展、胰岛素抵抗（IR）、脂质代谢失调或肾素-血管紧张素-醛固酮系统的过度激活。几种动物和培养细胞的研究证明，过氧化物酶体增殖物激活受体γ（PPARγ）异构体似乎在这种脂毒性的发展中发挥着重要作用。因此，PPARγ激动剂在肥胖相关 CKD 的治疗方法中具有重要意义。本综述旨在总结使用体内和体外模型的当前知识，重点关注 PPARγ，概述脂毒性影响肾脏结构和功能的机制。
