Abstract
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.
Highlights
The kidney is characterized by a complex anatomy, with millions of nephrons as the functional unit to excrete nitrogen waste and secure fluid homeostasis
Glomerular podocytes display much lower mitochondrial density than in proximal tubule epithelial cells (PTEC) and rely primarily on anaerobic glycolysis to maintain glomerular filtration barrier and are relatively insensitive to defect in mitochondrial biogenesis during ischemia damage (Brinkkoetter et al, 2019)
We summarize the recent advances in understanding lipid metabolism in the function of kidney mitochondria and the molecular mechanisms related to dyslipidemia during kidney disease progression
Summary
The kidney is characterized by a complex anatomy, with millions of nephrons as the functional unit to excrete nitrogen waste and secure fluid homeostasis. The kidney is composed of multiple specialized cell types ensuring vital homeostasis of acid-base and electrolyte balance, blood pressure regulation, nutrient reabsorption, and hormone secretion (Hoenig and Zeidel, 2014; Duann and Lin, 2017; Yu et al, 2019). It is one of the most metabolically active organs other than heart and skeletal muscle, with proximal tubules presenting a very high density of mitochondria required for energy consumption (Meyer et al, 1997; Wang et al, 2000)
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