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

18 Citations (Scopus)

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

Fingerprint

Swine
Tumor Necrosis Factor-alpha
Fats
Obesity
Kidney
Intra-Abdominal Fat
Renal Circulation
Renal Artery
Glomerular Filtration Rate
Blood Pressure
Sus scrofa
High Fat Diet
Fructose
Chronic Renal Insufficiency
Baths
Vasodilation
Acetylcholine
Endothelium
Macrophages
Cholesterol

Keywords

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

ASJC Scopus subject areas

  • Urology

Cite this

Perirenal Fat Promotes Renal Arterial Endothelial Dysfunction in Obese Swine through Tumor Necrosis Factor-α. / Ma, Shuangtao; Zhu, Xiang Yang; Eirin, Alfonso; Woollard, John R.; Jordan, Kyra L.; Tang, Hui; Lerman, Amir; Lerman, Lilach O.

In: Journal of Urology, 2016.

Research output: Contribution to journalArticle

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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.",
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AU - Jordan, Kyra L.

AU - Tang, Hui

AU - Lerman, Amir

AU - Lerman, Lilach O

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N2 - 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.

AB - 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.

KW - Adipose tissue

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KW - Tumor necrosis factor-alpha

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