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Review
. 2010 Jul;19(4):393-402.
doi: 10.1097/MNH.0b013e32833aa4ac.

Renal lipid metabolism and lipotoxicity

Ion Alexandru Bobulescu  1
Affiliations
Review

Renal lipid metabolism and lipotoxicity

Ion Alexandru Bobulescu. Curr Opin Nephrol Hypertens. 2010 Jul.

Abstract

Purpose of review: Lipid accumulation in nonadipose tissues is increasingly recognized to contribute to organ injury through a process termed lipotoxicity, but whether this process occurs in the kidney is still uncertain. This article briefly summarizes the normal role of lipids in renal physiology and the current evidence linking excess lipids and lipotoxicity to renal dysfunction.

Recent findings: Evidence suggesting that renal lipid accumulation and lipotoxicity may lead to kidney dysfunction has mounted significantly over recent years. Abnormal renal lipid content has been described in a number of animal models and has been successfully manipulated using pharmacologic or genetic strategies. There is some heterogeneity among studies with regard to the mechanisms, consequences, and localization of lipid accumulation in the kidney, explainable at least in part by inherent differences between animal models. The relevance of these findings for human pathophysiology remains to be established.

Summary: Current knowledge on renal lipid physiology and pathophysiology is insufficient, but provides a strong foundation and incentive for further exploration. The future holds significant challenges in this area, especially with regard to applicability of research findings to the human kidney in vivo, but also the opportunity to transform our understanding of an array of kidney disorders.

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Figures

Figure 1
Figure 1. Lipid accumulation in human kidney samples visualized by Oil Red O staining
Kidney surgical specimens were obtained from patients undergoing radical nephrectomy for renal cell carcinoma. Normal kidney cortex samples were dissected by an experienced pathologist, away from the tumor. The samples were frozen, sectioned, and stained with hematoxylin and Oil Red O to visualize the distribution of lipids within renal structures. Left panels are representative images from three different patients (original color images are shown here in gray scale). For each image, a computer-based color deconvolution algorithm was used to separately visualize Oil Red O staining in the red channel (right panels). In these examples, lipid deposits are localized mostly within tubular epithelial cells in patients 1 and 2, but are not detectable in patient 3.
Figure 2
Figure 2. Entry of free nonesterified fatty acids into proximal tubule cells and the role of albumin as ‘Trojan horse’
(a) Under normal conditions, fatty acids enter the proximal tubule cell from the basolateral side as well as from the apical (luminal) side, carried on albumin. Albumin is degraded in lysosomes, but transcytosis has also been proposed. Depending on cellular energy needs, intracellular fatty acids are directed to mitochondrial b-oxidation or to triglyceride stores. (b) Several conditions can theoretically lead to increased fatty acid intake into the proximal tubule cell, including high albumin filtration, high fatty acid to albumin molar ratio, and circulating lipid disturbances. These conditions, alone or in combination, may cause increased intracellular concentration of fatty acids, exceeding the b-oxidative capacity of mitochondria. This leads to intracellular accumulation of triglycerides and to the generation of lipid metabolites with potential toxic effect.
Figure 3
Figure 3. Fatty acids may affect proximal tubule ammonium production by mitochondrial substrate competition
Ammonium (NH4+) is produced in the proximal tubule by the metabolism of glutamine to α-ketoglutarate, which then continues in the Krebs cycle. The products of fatty acid β-oxidation also enter the Krebs cycle. Increased intracellular concentration of fatty acids may compete with glutamine as mitochondrial substrate, decreasing its utilization and reducing ammonium production.
See this image and copyright information in PMC

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