title: Obesity-metabolic derangement preserves hemodynamics but promotes intrarenal adiposity and macrophage infiltration in swine renovascular disease.
abstract: Obesity-metabolic disorders (ObM) often accompany renal artery stenosis (RAS). We hypothesized that the coexistence of ObM and RAS magnifies inflammation and microvascular remodeling in the stenotic kidney (STK) and aggravates renal scarring. Twenty-eight obesity-prone Ossabaw pigs were studied after 16 wk of a high-fat/high-fructose diet or standard chow including ObM-sham, ObM-RAS, Lean-RAS, or Lean-sham (normal control) groups. Single-kidney renal blood flow (RBF) and glomerular filtration rate (GFR) were assessed by multidetector computed tomography (CT), renal oxygenation and tubular transport capability by blood-oxygen-level-dependent MRI, and microcirculation by micro-CT for vessel density, and Western blotting for protein expressions of angiogenic factors (VEGF/FLK-1). Renal vein and inferior vena cava levels of inflammatory cytokines were measured to evaluate systemic and kidney inflammation. Macrophage (MØ) infiltration and subpopulations, fat deposition in the kidney, and inflammation in perirenal and abdominal fat were also examined. GFR and RBF were decreased in Lean-STK but relatively preserved in ObM-STK. However, ObM-STK showed impaired tubular transport function, suppressed microcirculation, and stimulated glomerulosclerosis. ObM diet interacted with RAS to blunt angiogenesis in the STK, facilitated the release of inflammatory cytokines, and led to greater oxidative stress than Lean-STK. The ObM diet also induced fat deposition in the kidney and infiltration of proinflammatory M1-MØ, as also in perirenal and abdominal fat. Coexistence of ObM and RAS amplifies renal inflammation, aggravates microvascular remodeling, and accelerates glomerulosclerosis. Increased adiposity and MØ-accentuated inflammation induced by an ObM diet may contribute to structural injury in the post-STK kidney.
authors: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
authors: Xin
authors: X
authors: Zhang
authors: Zi-Lun
authors: ZL
authors: Li
authors: John R
authors: JR
authors: Woollard
authors: Alfonso
authors: A
authors: Eirin
authors: Behzad
authors: B
authors: Ebrahimi
authors: John A
authors: JA
authors: Crane
authors: Xiang-Yang
authors: XY
authors: Zhu
authors: Aditya S
authors: AS
authors: Pawar
authors: James D
authors: JD
authors: Krier
authors: Kyra L
authors: KL
authors: Jordan
authors: Hui
authors: H
authors: Tang
authors: Stephen C
authors: SC
authors: Textor
authors: Amir
authors: A
authors: Lerman
authors: Lilach O
authors: LO
authors: Lerman
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D050154:Adiposity / Q000502:physiology*; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western; D016207:Cytokines / Q000378:metabolism; D005355:Fibrosis; D006439:Hemodynamics / Q000502:physiology*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007668:Kidney / Q000473:pathology*; D008264:Macrophages / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008833:Microcirculation / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000502:physiology; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology*; D018384:Oxidative Stress / Q000502:physiology; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000502:physiology; D012078:Renal Artery Obstruction / Q000473:pathology*; D012079:Renal Circulation / Q000502:physiology; D013552:Swine
chemical_list: D015415:Biomarkers; D016207:Cytokines; D010100:Oxygen
keywords: adiposity; inflammation; macrophage; obesity-metabolic derangement; renal artery stenosis
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