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Renal lipid accumulation, oxidative stress and uric acid handling in a rodent model of obesity and metabolic syndrome
  1. Tara R Rosenthal1,
  2. Sun K Park1,
  3. Subash Kairamkonda2,
  4. Sabiha Khatoon2,
  5. Laurentiu M Pop3,
  6. Ion Alexandru Bobulescu2,4
  1. 1Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA
  2. 2Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, Texas, USA
  3. 3Radiation Oncology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA
  4. 4Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas, USA
  1. Correspondence to Dr Ion Alexandru Bobulescu, Texas Tech University Health Sciences Center, Lubbock, TX 79409, USA; ion.a.bobulescu{at}ttuhsc.edu

Abstract

Hyperuricemia is more prevalent among people with obesity and metabolic syndrome, and is associated with adverse clinical outcomes. We hypothesized that increased renal reabsorption of uric acid (UA) in obesity and metabolic syndrome may be an adaptive response of the kidney when faced with fatty acid-induced oxidative stress. To test this hypothesis, we examined lipid accumulation, markers of oxidative stress, and renal UA handling in Zucker diabetic fatty (ZDF) rats, and in matched lean control animals. Rats were randomized to either normal rodent chow or a diet supplemented with antioxidants (α-tocopheryl acetate, sodium selenite, zinc sulfate, and ascorbic acid), and were followed up for either 4 or 20 weeks after randomization. Dietary antioxidant supplementation had no significant effects in lean control rats but led to partial improvement in markers of elevated oxidative stress in the kidney of ZDF rats. Renal UA handling was not affected by antioxidant supplementation. We observed robust correlations between renal lipid content and oxidative stress markers in the pooled experimental groups, particularly in older animals after 20 weeks on the study diets. Dietary antioxidant supplementation did not prevent the gradual decline in renal function observed in older ZDF rats. These findings suggest that hyperuricemia in the ZDF rat model of obesity and the metabolic syndrome is not caused by renal oxidative stress, that there may be a pathophysiological link between lipid accumulation and oxidative stress in the kidney, and that antioxidant supplementation does not prevent age-related decline in renal function in ZDF rats.

  • obesity
  • kidney diseases
  • antioxidants
  • lipids

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Footnotes

  • TRR and SKP contributed equally.

  • Contributors Conceived and designed experiments: IAB (guarantor). Performed experiments: TRR, SKP, LMP and IAB. Analyzed the data: TRR, SKP, LMP and IAB. Interpreted results: TRR, SKP, SKa, SKh, LMP and IAB. Drafted manuscript: SKa, SKh, LMP and IAB. Edited and revised the manuscript: SKa, SKh, LMP and IAB. Approved the final version: TRR, SKP, SKa, SKh, LMP and IAB.

  • Funding IAB was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK, grant R01-DK113377), with additional support from Southwestern Medical Foundation’s Haberecht Wild-Hare Idea Research Program. The UT Southwestern O'Brien Kidney Research Core Center was supported by NIDDK (grant P30-DK079328).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request.

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