Division of Nephrology and Endocrinology, the University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan.
Division of CKD Pathophysiology, the University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan.
Nutrients. 2019 Jul 20;11(7):1664. doi: 10.3390/nu11071664.
Dyslipidemia is a common nutritional and metabolic disorder in patients with chronic kidney disease. Accumulating evidence supports the hypothesis that prolonged metabolic imbalance of lipids leads to ectopic fat distribution in the peripheral organs (lipotoxicity), including the kidney, heart, and skeletal muscle, which accelerates peripheral inflammation and afflictions. Thus, lipotoxicity may partly explain progression of renal dysfunction and even extrarenal complications, including renal anemia, heart failure, and sarcopenia. Additionally, endoplasmic reticulum stress activated by the unfolded protein response pathway plays a pivotal role in lipotoxicity by modulating the expression of key enzymes in lipid synthesis and oxidation. Here, we review the molecular mechanisms underlying lipid deposition and resultant tissue damage in the kidney, heart, and skeletal muscle, with the goal of illuminating the nutritional aspects of these pathologies.
血脂异常是慢性肾脏病患者常见的营养代谢紊乱。越来越多的证据支持这样一种假说，即脂质代谢失衡时间延长会导致外周器官（脂毒性）异位脂肪分布，包括肾脏、心脏和骨骼肌，从而加速外周炎症和病变。因此，脂毒性可能部分解释了肾功能障碍甚至肾外并发症的进展，包括肾性贫血、心力衰竭和肌肉减少症。此外，未折叠蛋白反应途径激活的内质网应激通过调节脂质合成和氧化关键酶的表达在脂毒性中起关键作用。在这里，我们综述了脂质沉积和肾脏、心脏和骨骼肌组织损伤的分子机制，以期阐明这些病变的营养方面。
