title: Systemic upregulation of NADPH oxidase in diet-induced obesity in rats.
abstract: Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is upregulated in a variety of tissues in obesity. It is still unclear as to whether NADPH oxidase upregulation in a specific tissue is part of a systemic response. Here we analyzed the expression pattern of NADPH oxidase in  vascular, adipose, and kidney tissues in a rat model of diet-induced obesity. After weaning, rats were fed either a normal or high-fat diet for 12 weeks. The high-fat diet resulted in 20% increased body weight. In the aorta, Nox4 expression was increased by three-fold in obese rats. Upregulations  of p22phox and p47phox in adipose, and Nox4, p22phox, and p47phox in kidney were observed in obesity. Marked increases in plasma leptin and insulin were observed, with more modest changes in adiponectin in obese rats. The average systolic blood pressure in the obese group was 11 mmHg  higher than that of lean rats (P < 0.005). There was a significant correlation between blood pressure and aortic Nox4 expression (P < 0.01). In cultured vascular smooth muscle cells, adiponectin reduced the expression of Nox4 in a protein kinase A-dependent  manner. Our results suggest that upregulation of NADPH oxidase in multiple tissues during obesity appears to be a systemic response. At least in vitro, adiponectin may have a protective antioxidant role by suppressing vascular NADPH oxidase expression. The association between NADPH  oxidase Nox4 expression in the vasculature and the elevated blood pressure in obesity requires further investigation.
authors.affiliation: O'Brien Institute and Department of Surgery, University of Melbourne, Melbourne, Victoria, Australia. fjiang@sdu.edu.cn
authors.forename: Fan
authors.initials: F
authors.lastname: Jiang
authors.forename: Han K
authors.initials: HK
authors.lastname: Lim
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Morris
authors.forename: Larissa
authors.initials: L
authors.lastname: Prior
authors.forename: Elena
authors.initials: E
authors.lastname: Velkoska
authors.forename: Xiao
authors.initials: X
authors.lastname: Wu
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dusting
mesh_terms: D052242:Adiponectin / Q000494:pharmacology; D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001013:Aorta, Thoracic / Q000378:metabolism; D001794:Blood Pressure; D002478:Cells, Cultured; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D004789:Enzyme Activation; D007328:Insulin / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism*; D009765:Obesity / Q000209:etiology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation; D015430:Weight Gain
chemical_list: D052242:Adiponectin; C499920:Adipoq protein, rat; D000975:Antioxidants; D007328:Insulin; D020738:Leptin; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498911:Nox4 protein, rat; C515768:Cyba protein, rat; C060505:neutrophil cytosolic factor 1