scholarly journals Dysfunctional fatty acid oxidation in renal fibrosis

2014 ◽  
Vol 11 (2) ◽  
pp. 64-64 ◽  
Author(s):  
Susan J. Allison
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Renal Fibrosis ◽  
Acid Oxidation

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 Impairment of PPARα and the Fatty Acid Oxidation Pathway Aggravates Renal Fibrosis during Aging

2018 ◽  
Vol 29 (4) ◽  
pp. 1223-1237 ◽  
Author(s):  
Ki Wung Chung ◽  
Eun Kyeong Lee ◽  
Mi Kyung Lee ◽  
Goo Taeg Oh ◽  
Byung Pal Yu ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Epithelial Cells ◽  
Fatty Acid Oxidation ◽  
Calorie Restriction ◽  
Lipid Accumulation ◽  
Renal Fibrosis ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Effects Of Aging

Defects in the renal fatty acid oxidation (FAO) pathway have been implicated in the development of renal fibrosis. Although, compared with young kidneys, aged kidneys show significantly increased fibrosis with impaired kidney function, the mechanisms underlying the effects of aging on renal fibrosis have not been investigated. In this study, we investigated peroxisome proliferator–activated receptor α (PPARα) and the FAO pathway as regulators of age-associated renal fibrosis. The expression of PPARα and the FAO pathway–associated proteins significantly decreased with the accumulation of lipids in the renal tubular epithelial region during aging in rats. In particular, decreased PPARα protein expression associated with increased expression of PPARα-targeting microRNAs. Among the microRNAs with increased expression during aging, miR-21 efficiently decreased PPARα expression and impaired FAO when ectopically expressed in renal epithelial cells. In cells pretreated with oleic acid to induce lipid stress, miR-21 treatment further enhanced lipid accumulation. Furthermore, treatment with miR-21 significantly exacerbated the TGF-β–induced fibroblast phenotype of epithelial cells. We verified the physiologic importance of our findings in a calorie restriction model. Calorie restriction rescued the impaired FAO pathway during aging and slowed fibrosis development. Finally, compared with kidneys of aged littermate controls, kidneys of aged PPARα−/− mice showed exaggerated lipid accumulation, with decreased activity of the FAO pathway and a severe fibrosis phenotype. Our results suggest that impaired renal PPARα signaling during aging aggravates renal fibrosis development, and targeting PPARα is useful for preventing age-associated CKD.

Glucocorticoids promote mitochondrial fatty acid oxidation in the fetal heart

2019 ◽  
Author(s):  
Helena Urquijo ◽  
Emma N Panting ◽  
Roderick N Carter ◽  
Emma J Agnew ◽  
Caitlin S Wyrwoll ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Fetal Heart ◽  
Acid Oxidation ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Mitochondrial Fatty Acid

Recognition and management of fatty acid oxidation defects: A series of 107 patients

1999 ◽  
Vol 22 (4) ◽  
pp. 487-502 ◽  
Author(s):  
J. M. Saudubray ◽  
D. Martin ◽  
P. De Lonlay ◽  
G. Touati ◽  
F. Poggi-Travert ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Acid Oxidation
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