title: Renal protective effects of induction of haem oxygenase-1 combined with increased adiponectin on the glomerular vascular endothelial growth factor-nitric oxide axis in obese rats.
abstract: What is the central question of this study? This study aimed to investigate whether induction of haem oxygenase-1 (HO-1) can protect the kidneys of obese rats by regulating the glomerular vascular endothelial growth factor-nitric oxide (VEGF-NO) axis by increasing the adiponectin concentrations. What is the main finding and its importance? Induction of HO-1 reduces the degree of microalbuminuria and has renal protective effects by improving endothelial function and regulating the uncoupled glomerular VEGF-NO axis in diet-induced obese rats. The mechanism may be related to increased activation of the HO-1-adiponectin axis. The glomerular vascular endothelial growth factor-nitric oxide (VEGF-NO) axis plays a critical role in maintenance of normal kidney function in obesity. Induction of haem oxygenase-1 (HO-1) may result in a parallel increase in adiponectin secretion. The aim of this study was to investigate whether induction of HO-1 could protect the kidneys of obese rats by regulating the glomerular VEGF-NO axis by increasing adiponectin levels. Rats received high-fat diets and were injected with either cobalt protoporphyrin to induce HO-1 or stannous protoporphyrin to inhibit HO-1. Blood and urine samples were collected. Endothelial function was determined by measuring the endothelium-dependent vasodilatation of the aorta. Renal tissues were collected for CD34 immunohistochemistry. The glomerular VEGF-NO axis and the AMP kinase-phosphoinositide 3-kinase (PI3K)/Akt-endothelial nitric oxide synthase pathway were measured. Induction of HO-1 by cobalt protoporphyrin decreased microalbuminuria, plasma free fatty acids, serum high-sensitivity C-reactive protein and malondialdehyde levels and increased serum adiponectin levels compared with the untreated obese rats. Severe impairment of endothelium-dependent vasodilatation was observed in the obese rats, which was improved to some extent by HO-1 induction. Induction of HO-1 reduced glomerular CD34 expression and production of reactive oxygen species in obese rats. Obese rats showed increased glomerular VEGF expression and reduced NO levels. This uncoupling of the glomerular VEGF-NO axis was improved to some extent by induction of HO-1, with enhancement of p-AMP kinase, p-Akt and phospho-endothelial nitric oxide synthase in obese rats. These results indicate that induction of HO-1 with cobalt protoporphyrin reduces the degree of microalbuminuria and has renal protective effects by improving endothelial dysfunction and regulating the glomerular VEGF-NO axis in diet-induced obese rats by increasing adiponectin levels.
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Weifang Medical University, Weifang, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Public Health Management, Affiliated Hospital of Weifang Medical University, Weifang, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zang
authors.affiliation: Department of Pathology, Affiliated Hospital of Weifang Medical University, Weifang, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Han
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Weifang Medical University, Weifang, China.
authors.forename: Ningning
authors.initials: N
authors.lastname: Hou
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Weifang Medical University, Weifang, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Sun
mesh_terms: D052242:Adiponectin / Q000378:metabolism*; D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000098:blood supply / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009765:Obesity / Q000378:metabolism; D017208:Rats, Wistar; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D052242:Adiponectin; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D051547:Heme Oxygenase-1