title: Perirenal Fat Promotes Renal Arterial Endothelial Dysfunction in Obese Swine through Tumor Necrosis Factor-α.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota; Department of Cardiology, Chengdu Military General Hospital, Chengdu, Sichuan, People's Republic of China.
authors.forename: Shuangtao
authors.initials: S
authors.lastname: Ma
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota.
authors.forename: Xiang-Yang
authors.initials: XY
authors.lastname: Zhu
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Eirin
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota.
authors.forename: John R
authors.initials: JR
authors.lastname: Woollard
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota.
authors.forename: Kyra L
authors.initials: KL
authors.lastname: Jordan
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota.
authors.forename: Hui
authors.initials: H
authors.lastname: Tang
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota.
authors.forename: Amir
authors.initials: A
authors.lastname: Lerman
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota; Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota. Electronic address: lerman.lilach@mayo.edu.
authors.forename: Lilach O
authors.initials: LO
authors.lastname: Lerman
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D050152:Intra-Abdominal Fat / Q000503:physiopathology*; D007668:Kidney; D009765:Obesity / Q000503:physiopathology*; D012077:Renal Artery / Q000503:physiopathology*; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D014409:Tumor Necrosis Factor-alpha
keywords: adipose tissue; kidney; renal artery; renal insufficiency, chronic; tumor necrosis factor-alpha