Lin Pei-Hui, Duann Pu
Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, United States.
Research and Development, Salem Veteran Affairs Medical Center, Salem, VA, United States.
Front Physiol. 2020 Sep 3;11:1050. doi: 10.3389/fphys.2020.01050. eCollection 2020.
To excrete body nitrogen waste and regulate electrolyte and fluid balance, the kidney has developed into an energy factory with only second to the heart in mitochondrial content in the body to meet the high-energy demand and regulate homeostasis. Energy supply from the renal mitochondria majorly depends on lipid metabolism, with programed enzyme systems in fatty acid β-oxidation and Krebs cycle. Renal mitochondria integrate several metabolic pathways, including AMPK/PGC-1α, PPARs, and CD36 signaling to maintain energy homeostasis for dynamic and static requirements. The pathobiology of several kidney disorders, including diabetic nephropathy, acute and chronic kidney injuries, has been primarily linked to impaired mitochondrial bioenergetics. Such homeostatic disruption in turn stimulates a pathological adaptation, with mitochondrial enzyme system reprograming possibly leading to dyslipidemia. However, this alteration, while rescuing oncotic pressure deficit secondary to albuminuria and dissipating edematous disorder, also imposes an ominous lipotoxic consequence. Reprograming of lipid metabolism in kidney injury is essential to preserve the integrity of kidney mitochondria, thereby preventing massive collateral damage including excessive autophagy and chronic inflammation. Here, we review dyslipidemia in kidney disorders and the most recent advances on targeting mitochondrial energy metabolism as a therapeutic strategy to restrict renal lipotoxicity, achieve salutary anti-edematous effects, and restore mitochondrial homeostasis.
为了排泄体内含氮废物并调节电解质和液体平衡，肾脏已发展成为一个能量工厂，其线粒体含量在体内仅次于心脏，以满足高能量需求并调节体内平衡。肾脏线粒体的能量供应主要依赖脂质代谢，脂肪酸β-氧化和三羧酸循环中存在程序化的酶系统。肾脏线粒体整合了多种代谢途径，包括AMPK/PGC-1α、PPARs和CD36信号通路，以维持能量稳态，满足动态和静态需求。包括糖尿病肾病、急性和慢性肾损伤在内的几种肾脏疾病的病理生物学主要与线粒体生物能量学受损有关。这种体内平衡的破坏反过来会刺激一种病理适应性变化，线粒体酶系统的重新编程可能导致血脂异常。然而，这种改变在挽救继发于蛋白尿的胶体渗透压不足和消除水肿性疾病的同时，也带来了不祥的脂毒性后果。肾脏损伤时脂质代谢的重新编程对于维持肾脏线粒体的完整性至关重要，从而防止包括过度自噬和慢性炎症在内的大量附带损害。在此，我们综述了肾脏疾病中的血脂异常以及靶向线粒体能量代谢作为一种治疗策略来限制肾脏脂毒性、实现有益的抗水肿作用和恢复线粒体稳态的最新进展。
