scholarly journals Increased Fatty Acid Oxidation in Differentiated Proximal Tubular Cells Surviving a Reversible Episode of Acute Kidney Injury

2018 ◽  
Vol 47 (4) ◽  
pp. 1338-1351 ◽  
Author(s):  
Aurélien Bataille ◽  
Pierre Galichon ◽  
Nadjim Chelghoum ◽  
Badreddine Mohand Oumoussa ◽  
Marie-Julia Ziliotis ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
High Throughput ◽  
Renal Fibrosis ◽  
Kidney Injury ◽  
Proximal Tubules ◽  
Acid Oxidation ◽  
Renal Tubules ◽  
Sham Surgery

Background/Aims: Fatty acid oxidation (FAO), the main source of energy produced by tubular epithelial cells in the kidney, was found to be defective in tubulo-interstitial samples dissected out in kidney biopsies from patients with chronic kidney disease (CKD). Experimental data indicated that this decrease was a strong determinant of renal fibrogenesis, hence a focus for therapeutic interventions. Nevertheless, whether persistently differentiated renal tubules, surviving in a pro-fibrotic environment, also suffer from a decrease in FAO, is currently unknown. Methods: To address this question, we isolated proximal tubules captured ex vivo on the basis of the expression of an intact brush border antigen (Prominin-1) in C57BL6/J mice subjected to a controlled, two-hit model of renal fibrosis (reversible ischemic acute kidney injury (AKI) or sham surgery, followed by angiotensin 2 administration). A transcriptomic high throughput sequencing was performed on total mRNA from these cells, and on whole kidneys. Results: In contrast to mice subjected to sham surgery, mice with a history of AKI displayed histologically more renal fibrosis when exposed to angiotensin 2. High throughput RNA sequencing, principal component analysis and clustering showed marked consistency within experimental groups. As expected, FAO transcripts were decreased in whole fibrotic kidneys. Surprisingly, however, up- rather than down-regulation of metabolic pathways (oxidative phosphorylation, fatty acid metabolism, glycolysis, and PPAR signalling pathway) was a hallmark of the differentiated tubules captured from fibrotic kidneys. Immunofluorescence co-staining analysis confirmed that the expression of FAO enzymes was dependent of tubular trophicity. Conclusions: These data suggest that in differentiated proximal tubules energetic hyperactivity is promoted concurrently with organ fibrogenesis.

scholarly journals Sugar or Fat? Renal Tubular Metabolism Reviewed in Health and Disease

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1580
Author(s):  
Leslie S. Gewin
Keyword(s):  
Chronic Kidney Disease ◽  
Fatty Acid ◽  
Kidney Disease ◽  
Fatty Acid Oxidation ◽  
Kidney Injury ◽  
Proximal Tubules ◽  
Acid Oxidation ◽  
Renal Tubules ◽  
Solute Movement ◽  
Renal Tubular

The kidney is a highly metabolically active organ that relies on specialized epithelial cells comprising the renal tubules to reabsorb most of the filtered water and solutes. Most of this reabsorption is mediated by the proximal tubules, and high amounts of energy are needed to facilitate solute movement. Thus, proximal tubules use fatty acid oxidation, which generates more adenosine triphosphate (ATP) than glucose metabolism, as its preferred metabolic pathway. After kidney injury, metabolism is altered, leading to decreased fatty acid oxidation and increased lactic acid generation. This review discusses how metabolism differs between the proximal and more distal tubular segments of the healthy nephron. In addition, metabolic changes in acute kidney injury and chronic kidney disease are discussed, as well as how these changes in metabolism may impact tubule repair and chronic kidney disease progression.

Cyclophilin D Sequesters PPARα in Mitochondria to Impair Fatty Acid Oxidation in Cisplatin‐induced Acute Kidney Injury

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Babu J. Padanilam ◽  
Mi Ra Noh ◽  
LiGyeom Ha ◽  
Jinu Kim ◽  
Hee-Seong Jang
Keyword(s):  
Acute Kidney Injury ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Kidney Injury ◽  
Acid Oxidation ◽  
Cyclophilin D

scholarly journals Proximal tubule cyclophilin D regulates fatty acid oxidation in cisplatin-induced acute kidney injury

2020 ◽  
Vol 97 (2) ◽  
pp. 327-339 ◽  
Author(s):  
Hee-Seong Jang ◽  
Mi Ra Noh ◽  
Eui-Man Jung ◽  
Woo-Yang Kim ◽  
Siddesh Southekal ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Fatty Acid ◽  
Proximal Tubule ◽  
Fatty Acid Oxidation ◽  
Kidney Injury ◽  
Acid Oxidation ◽  
Cyclophilin D

MO328ASYMPTOMATIC HYPERURICEMIA ACTS AS ANTIOXIDANT DURING ACUTE KIDNEY INJURY AND DISEASE*

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Qiuyue Ma ◽  
Viviane Gnemmi ◽  
Anders Hans-Joachim ◽  
Stefanie Steiger
Keyword(s):  
Acute Kidney Injury ◽  
Fatty Acid ◽  
Epithelial Cells ◽  
Kidney Function ◽  
Metabolic Activity ◽  
Mitochondrial Biogenesis ◽  
Kidney Injury ◽  
Acid Oxidation ◽  
Tubular Epithelial Cells ◽  
Tubular Injury

Abstract Background and Aims Acute kidney injury (AKI) and disease (AKD) are major causes of morbidity and mortality worldwide. Hyperuricemia (HU) is common in patients with impaired kidney function. While there is no doubt that crystalline uric acid (UA) causes acute and chronic UA nephropathy, urolithiasis and kidney stone disease, the pathogenesis of asymptomatic HU in AKI/AKD is incompletely understood. In animal studies, elevated serum UA levels may lead to endothelial dysfunction, renin-angiotensin system activation and oxidative stress. However, such models do not mimic human HU. To overcome this issue, we established a model of AKI/AKD with clinically relevant serum UA levels and hypothesized that asymptomatic HU improves the outcomes after AKI/AKD by restoring metabolic activity and mitochondrial biogenesis in macrophages and tubular epithelial cells. Method Alb-creERT2;Glut9lox/lox and Glut9lox/lox control mice were injected with tamoxifen and placed on a chow diet enriched with inosine. Hyperuricemic mice (serum UA ≥7 mg/dL) and mice without HU (serum UA 4-5 mg/dL) underwent uninephrectomy followed by unilateral ischemia-reperfusion (IR) to induce AKI/AKD. Serum and kidneys were collected on day 3 and 14 after AKI/AKD, and kidney function, tubular injury, inflammation, mitochondrial dysfunction, metabolic activity (fatty acid oxidation) and macrophage infiltration were quantified using GFR measurement, immunohistochemistry, colorimetric assays, electron microscopy, RT-PCR and flow cytometry. Results We observed an increase in serum UA levels from 7 to 10 mg/dL in hyperuricemic mice on day 3 after IR-induced AKI/AKD that returned to 7 mg/dL after 14 days (Figure left). While there was no difference in GFR between hyperuricemic and mice without HU with AKI/AKD on day 3, we found an improved kidney function in hyperuricemic mice on day 14 (Figure middle). This was associated with significantly less tubular injury and inflammation as well as an increase in the number of infiltrating anti-inflammatory M2-like macrophages as compared to mice without HU. Intrarenal mRNA expression level of the pro-oxidant heme-oxygenase-1 was reduced in hyperuricemic mice. However, the expression of anti-oxidant enzymes (Nrf-1 and Sod) and metabolic genes associated with fatty acid oxidation (Cpt1, Pparg, and Pgc1b) significantly increased as compared to mice without HU 14 days after AKI/AKD. In addition, HU increased the number of phospho-Histone-3 and intact proximal tubules and restored tubular mitochondrial morphology as indicated by an increased mitochondrial aspect ratio (Figure right). Conclusion Our data imply that asymptomatic HU improves kidney outcomes after IR-induced AKI/AKD because HU attenuates tubular injury and inflammation. In addition, we found that HU enhances the metabolic activity and anti-inflammatory M2-like macrophage polarization as well as restores mitochondrial biogenesis in tubular epithelial cells, suggesting that HU acts as antioxidant by improving kidney recovery after AKI/AKD.

Pathogenesis of Acute Kidney Injury

2019 ◽  
pp. 11-20
Author(s):  
David P. Basile ◽  
Babu J. Padanilam
Keyword(s):  
Acute Kidney Injury ◽  
Cell Death ◽  
Renal Function ◽  
Fatty Acid ◽  
Interstitial Fibrosis ◽  
Kidney Injury ◽  
Acid Oxidation ◽  
Clinical Disorder ◽  
Successful Recovery ◽  
Multiple Issues

Acute kidney injury represents a significant clinical disorder associated with a rapid loss of renal function following a variety of potential insults. This chapter reviews multiple issues related to the pathophysiology of AKI with an emphasis on studies from animal models. Early responses following kidney injury include impaired hemodynamic and bioenergetic responses. Reductions in renal ATP levels occur as a result of compromised fatty acid oxidation and impaired compensation by glycolysis. Sustained reductions in perfusion contribute to extension of AKI characterized by complex inflammatory and cellular injury responses, often leading to cell death. Concurrently, the kidney displays an elegant repair response, leading to successful recovery in most cases, characterized in part by epithelial cell growth, while maladaptive or incomplete recovery of tubules or capillaries can predispose the development of interstitial fibrosis and CKD progression.

scholarly journals Evolution of altered tubular metabolism and mitochondrial function in sepsis-associated acute kidney injury

2020 ◽  
Vol 319 (2) ◽  
pp. F229-F244
Author(s):  
Ying Li ◽  
Noureddin Nourbakhsh ◽  
Hai Pham ◽  
Rick Tham ◽  
Jonathan E. Zuckerman ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Mitochondrial Function ◽  
Cecal Ligation ◽  
Kidney Injury ◽  
Proximal Tubules ◽  
Metabolic Reprogramming ◽  
Acid Oxidation ◽  
Mitochondrial Content ◽  
Major Barrier ◽  
Renal Oxygen

Sepsis-associated acute kidney injury (s-AKI) has a staggering impact in patients and lacks any treatment. Incomplete understanding of the pathogenesis of s-AKI is a major barrier to the development of effective therapies. We address the gaps in knowledge regarding renal oxygenation, tubular metabolism, and mitochondrial function in the pathogenesis of s-AKI using the cecal ligation and puncture (CLP) model in mice. At 24 h after CLP, renal oxygen delivery was reduced; however, fractional oxygen extraction was unchanged, suggesting inefficient renal oxygen utilization despite decreased glomerular filtration rate and filtered load. To investigate the underlying mechanisms, we examined temporal changes in mitochondrial function and metabolism at 4 and 24 h after CLP. At 4 h after CLP, markers of mitochondrial content and biogenesis were increased in CLP kidneys, but mitochondrial oxygen consumption rates were suppressed in proximal tubules. Interestingly, at 24 h, proximal tubular mitochondria displayed high respiratory capacity, but with decreased mitochondrial content, biogenesis, fusion, and ATP levels in CLP kidneys, suggesting decreased ATP synthesis efficiency. We further investigated metabolic reprogramming after CLP and observed reduced expression of fatty acid oxidation enzymes but increased expression of glycolytic enzymes at 24 h. However, assessment of functional glycolysis revealed lower glycolytic capacity, glycolytic reserve, and compensatory glycolysis in CLP proximal tubules, which may explain their susceptibility to injury. In conclusion, we demonstrated significant alterations in renal oxygenation, tubular mitochondrial function, and metabolic reprogramming in s-AKI, which may play an important role in the progression of injury and recovery from AKI in sepsis.

scholarly journals The Link Between the Mitochondrial Fatty Acid Oxidation Derangement and Kidney Injury

2020 ◽  
Vol 11 ◽  
Author(s):  
Lara Console ◽  
Mariafrancesca Scalise ◽  
Nicola Giangregorio ◽  
Annamaria Tonazzi ◽  
Maria Barile ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Kidney Injury ◽  
Acid Oxidation ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Mitochondrial Fatty Acid
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