High-Fat Diet Increased Oxidative Stress and Mitochondrial Dysfunction Induced by Renal Ischemia-Reperfusion Injury in Rat.

Priyanka N Prem,Gino A Kurian

doi:10.3389/fphys.2021.715693

Abstract

Renal ischemia-reperfusion (IR) injury is one of the major causes of acute kidney injury influenced by the ischemic duration and the presence of comorbidities. Studies have reported that high-fat diet consumption can induce renal lipotoxicity and metabolic dyshomeostasis that can compromise the vital functions of kidney. This study aimed to evaluate the impact of a high-fat diet in the recovery of renal tissue from IR and explored the cellular pathology. In this study, 24 male Wistar rats were divided into two groups: normal diet (ND; n = 12) and high-fat diet (HD; n = 12), which were further subdivided into sham and IR groups at the end of the dietary regimen. The high-fat diet was introduced in 4-week-old rats and continued for 16 weeks. IR was induced by bilateral clamping of the renal peduncle for 45 min, followed by 24 h of reperfusion. Blood chemistry, estimated glomerular filtration rate (eGFR), mitochondrial function, and oxidative stress analysis were carried out to study the pathological changes. The rats fed with HD showed a decreased eGFR and elevated plasma creatinine, thereby compromised kidney function. Subcellular level changes in HD rats are deceased mitochondrial copy number, low PGC-1α gene expression, and declined electron transport chain (ETC) enzymes and adenosine triphosphate (ATP) level. Upon IR induction, HD rats exhibited severely impaired renal function (eGFR-0.09 ml/min) and elevated injury markers compared with ND rats. A histological analysis displayed increased tubular necrosis and cast formation in HD-IR in comparison to ND-IR. The oxidative stress and mitochondrial dysfunction were more prominent in HD-IR. In vitro protein translation assessment revealed impaired translational capacity in HD-IR mitochondria, which suggests mitochondrial changes with diet that may adversely affect the outcome of IR injury. High-fat diet consumption alters the normal renal function by modifying the cellular mitochondria. The renal changes compromise the ability of the kidney to recover from ischemia during reperfusion.

Highlights

Diet, designed for the kidney, can be promote its health and slow down its progression to failure (Rysz et al, 2017)
To assess whether the mitochondrial copy number plays a significant role in the reduced functional activity, we evaluated the mitochondrial copy number in the rat renal tissues from all the experimental groups and noticed a significant (P < 0.05) reduction in the copy number in high-fat diet (HD) treated rats compared to the normal diet (ND)-fed animals (Figure 4A)
We provide evidence for the deleterious effect in rat fed with HD based on the renal function, such as low glomerular filtration rate (GFR), low tissue mitochondrial activities, reduced copy number, and altered mitochondrial gene expression from rats treated with a normal diet

Summary

Introduction

Designed for the kidney, can be promote its health and slow down its progression to failure (Rysz et al, 2017). Diet rich in high fat is common in many countries and can contribute to the development and progression of non-communicable diseases, such as cardiovascular diseases, Alzheimer’s disease, and acute and chronic kidney injury (World Health Organization, 2010). HD is reported to induce glomerulopathy and proximal convoluted tubule injury in kidney (Szeto et al, 2016). It can impact lysosomal dysfunction and impaired autophagy (Yamamoto et al, 2017). Nephrons are rich in mitochondria, HD-linked renal tubular cell injury and alterations in glomeruli, fibrosis, and podocyte damage that can promote the transition of acute to chronic kidney injury may be associated with mitochondrial function (Sun et al, 2020)

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