Perirenal Fat Promotes Renal Arterial Endothelial Dysfunction in Obese Swine through Tumor Necrosis Factor-α

Shuangtao Ma, Xiang Yang Zhu, Alfonso Eirin, John R. Woollard, Kyra L. Jordan, Hui Tang, Amir Lerman, Lilach O Lerman

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Purpose: Perirenal fat is associated with poor blood pressure control and chronic kidney disease but the underlying mechanisms remain elusive. We tested the hypothesis that perirenal fat impairs renal arterial endothelial function in pigs with obesity-metabolic derangements. Materials and Methods: We studied 14 domestic pigs after 16 weeks of a high fat/high fructose diet (obesity-metabolic derangement group) or standard chow (lean group). Renal blood flow, glomerular filtration rate and visceral fat volumes were studied in vivo by computerized tomography. Renal arterial endothelial function was also studied ex vivo in organ baths. Results: Pigs with obesity-metabolic derangements demonstrated increased body weight, blood pressure, cholesterol and intra-abdominal fat compared to lean pigs and perirenal fat volume was significantly larger. Renal blood flow and glomerular filtration rate were markedly elevated while urinary protein level was preserved. Ex vivo acetylcholine induced, endothelium dependent vasodilation of renal artery rings was substantially impaired in pigs with obesity-metabolic derangements compared to lean pigs. Endothelial function was further blunted in obesity-metabolic derangement and lean arterial rings by incubation with perirenal fat harvested from pigs with obesity-metabolic derangements but not from lean pigs. It was restored by inhibiting tumor necrosis factor-α. Perirenal fat from pigs with obesity-metabolic derangements also showed increased pro-inflammatory macrophage infiltration and tumor necrosis factor-α expression. Conclusions: In pigs with obesity-metabolic derangements perirenal fat directly causes renal artery endothelial dysfunction, which is partly mediated by tumor necrosis factor-α.

Original languageEnglish (US)
JournalJournal of Urology
DOIs
StateAccepted/In press - 2016

Keywords

  • Adipose tissue
  • Kidney
  • Renal artery
  • Renal insufficiency, chronic
  • Tumor necrosis factor-alpha

ASJC Scopus subject areas

  • Urology

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