Evaluation of iNOS inhibition on kidney function and structure in high-fat diet-induced kidney disease

Abstract

Background

Central obesity is related to caloric excess promoting deleterious cellular responses in targeted organs. Nitric oxide (NO) has been determined as a key player in the pathogenesis of metabolic diseases. Here, we investigated the implication of inducible NO synthase (iNOS) in the development of obesity-induced kidney disease.

Materials and Methods

C57Bl/6 male mice were randomized to a low-fat diet (LFD) or a high-fat diet (HFD) and treated with L-NIL, a specific iNOS inhibitor for 16 weeks.

Results

Mice fed a HFD exhibited a significant increase in body weight, fasting blood glucose, plasma levels of NEFA, triglyceride and insulin. iNOS inhibition prevented these changes in mice fed a HFD. Interestingly, the significant increase in albuminuria and mesangial matrix expansion were not ameliorated with L-NIL whereas a significant decrease in proteinuria, NAG (N-acetyl-ß-D-glucosaminidase) excretion and renal triglycerides content were found, suggesting that iNOS inhibition is more suitable for tubular function than glomerular function. The urinary hydrogen peroxide level, a stable product of ROS production, that was found to be increased in mice fed a HFD, was significantly reduced with L-NIL. Finally, despite a moderate effect of L-NIL on inflammatory process in the kidney, we demonstrated a positive impact of this treatment on adipocyte hypertrophy and on adipose tissue inflammation.

Conclusions

These results suggest that inhibition of iNOS leads to a moderate beneficial effect on kidney function in mice fed a HFD. Further studies are needed for better understanding of the role of iNOS in obesity-induced kidney disease.

This article is protected by copyright. All rights reserved

http://ift.tt/2fMI1z7