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High-fat diet consumption led to increased body and kidney weights, impaired glucose tolerance, hyperinsulinemia, polyuria, a 2.7-fold increase in 24-h urinary albumin excretion, 20% increase in renal glomerular volume, 18% increase in renal collagen deposition, and 8% drop of glomerular podocytes. It also resulted in a 5.3-fold increase in urinary 8-isoprostane excretion and a 38% increase in renal cortex 4-hydroxynonenal adduct accumulation. 4-hydroxynonenal adduct level and immunoreactivity or Sirtuin 1 expression in renal medulla were not affected. Studies of potential mechanisms of the high-fat diet induced renal cortex oxidative injury revealed that whereas nicotinamide adenine dinucleotide phosphate reduced form oxidase activity only tended to increase, 12\/15-lipoxygenase was significantly up-regulated, with approximately 12% increase in the enzyme protein expression and approximately 2-fold accumulation of 12(S)-hydroxyeicosatetraenoic acid, a marker of 12\/15-lipoxygenase activity. Accumulation of periodic acid-Schiff -positive material, concentrations of TGF-\u03b2, sorbitol pathway intermediates, and expression of nephrin, CAAT\/enhancer-binding protein homologous protein, phosphoeukaryotic initiation factor-\u03b1, and total eukaryotic initiation factor-\u03b1 in the renal cortex were indistinguishable between experimental groups. Vascular endothelial growth factor concentrations were reduced in high-fat diet fed mice. In conclusion, systemic and renal cortex oxidative stress associated with 12\/15-lipoxygenase overexpression and activation is an early phenomenon caused by high-calorie\/high-fat diet consumption and a likely contributor to kidney disease associated with prediabetes and alimentary obesity.<\/jats:p>","DOI":"10.1210\/en.2011-1997","type":"journal-article","created":{"date-parts":[[2012,1,11]],"date-time":"2012-01-11T01:32:56Z","timestamp":1326245576000},"page":"1152-1161","source":"Crossref","is-referenced-by-count":43,"title":["Prediabetic Nephropathy as an Early Consequence of the High-Calorie\/High-Fat Diet: Relation to Oxidative Stress"],"prefix":"10.1210","volume":"153","author":[{"given":"Hanna","family":"Shevalye","sequence":"first","affiliation":[{"name":"Pennington Biomedical Research Center (H.S., S.L., P.W., R.S., I.G.O.), Louisiana State University System, Baton Rouge, Louisiana 70808"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey","family":"Lupachyk","sequence":"first","affiliation":[{"name":"Pennington Biomedical Research Center (H.S., S.L., P.W., R.S., I.G.O.), Louisiana State University System, Baton Rouge, Louisiana 70808"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Watcho","sequence":"first","affiliation":[{"name":"Pennington Biomedical Research Center (H.S., S.L., P.W., R.S., I.G.O.), Louisiana State University System, Baton Rouge, Louisiana 70808"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Stavniichuk","sequence":"first","affiliation":[{"name":"Pennington Biomedical Research Center (H.S., S.L., P.W., R.S., I.G.O.), Louisiana State University System, Baton Rouge, Louisiana 70808"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaled","family":"Khazim","sequence":"first","affiliation":[{"name":"Department of Medicine (K.K., H.E.A.), Division of Nephrology, University of Texas Health Science Center, San Antonio, Texas 78229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna E.","family":"Abboud","sequence":"first","affiliation":[{"name":"Department of Medicine (K.K., H.E.A.), Division of Nephrology, University of Texas Health Science Center, San Antonio, Texas 78229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina G.","family":"Obrosova","sequence":"first","affiliation":[{"name":"Pennington Biomedical Research Center (H.S., S.L., P.W., R.S., I.G.O.), Louisiana State University System, Baton Rouge, Louisiana 70808"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071612104072700_B1","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/nm0106-62","article-title":"Epidemiologic and economic consequences of the global epidemics of obesity and diabetes.","volume":"12","author":"Yach","year":"2006","journal-title":"Nat Med"},{"key":"2020071612104072700_B2","first-page":"463","article-title":"The metabolic syndrome in patients with type 1 diabetes mellitus. 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