title: Influence of a High-Fat Diet on Cardiac iNOS in Female Rats.
abstract: BACKGROUND
  Overexpression of inducible nitric oxide synthase (iNOS) is a key link between high-fat (HF) diet induced obesity and cardiovascular disease. Oestradiol has cardioprotective effects that may be mediated through reduction of iNOS activity/expression.
  
  
  METHODS
  In the present study, female Wistar rats were fed a standard diet or a HF diet (42% fat) for 10 weeks. iNOS gene and protein expressions were measured in heart tissue. HF-fed rats exhibited a significant increase in cardiac iNOS mRNA by 695% (p<.05), iNOS protein level by 248% (p<0.01), without changes in nitrate/nitrite levels. Expression of CD36 protein in plasma membranes was increased by 37% (p<0.05), while the concentration of free fatty acids (FFA) was reduced by 25% (p<0.01) in HF-fed rats. Expression of the p50 subunit of nuclear factor-kB (NFkB-p50) in heart was increased by 77% (p<0.01) in HF-fed rats. Expression of protein kinase B (Akt) and extracellular signalregulated kinases 1/2 (ERK1/2) were unchanged between the groups. There was a significant increase in the ratio of phospho-Akt/total Akt but not for phospho-ERK1/2/total ERK1/2 in HF-fed rats. Estrogen receptor-α levels (by 50%; p<0.05) and serum oestradiol concentrations (by 35%; p<0.05) were shown to be significantly reduced in HF-fed rats.
  
  
  CONCLUSIONS
  Our results revealed that a HF diet led to increased iNOS expression, most likely via a mechanism involving Akt and NFκB-p50 proteins. Decreased levels of oestradiol and ERα protein in the HF-fed group, in combination with increased iNOS levels are consistent with the hypothesis that oestradiol has a cardioprotective effect through its ability to regulate iNOS expression.
authors: Laboratory of Radiobiology and Molecular Genetics, Institute of Nuclear Sciences Vinca, University of Belgrade, Mike Petrovica Alasa 12-14, 11000 Belgrade. Serbia.
authors: Aleksandra
authors: A
authors: Jovanovic
authors: Laboratory of Radiobiology and Molecular Genetics, Institute of Nuclear Sciences Vinca, University of Belgrade, Mike Petrovica Alasa 12-14, 11000 Belgrade. Serbia.
authors: Emina
authors: E
authors: Sudar-Milovanovic
authors: Laboratory of Radiobiology and Molecular Genetics, Institute of Nuclear Sciences Vinca, University of Belgrade, Mike Petrovica Alasa 12-14, 11000 Belgrade. Serbia.
authors: Milan
authors: M
authors: Obradovic
authors: School of Medicine, University of St Andrews, St Andrews, KY16 9TF. United Kingdom.
authors: Samantha J
authors: SJ
authors: Pitt
authors: School of Medicine, University of St Andrews, St Andrews, KY16 9TF. United Kingdom.
authors: Alan J
authors: AJ
authors: Stewart
authors: Laboratory of Radiobiology and Molecular Genetics, Institute of Nuclear Sciences Vinca, University of Belgrade, Mike Petrovica Alasa 12-14, 11000 Belgrade. Serbia.
authors: Sonja
authors: S
authors: Zafirovic
authors: Laboratory of Radiobiology and Molecular Genetics, Institute of Nuclear Sciences Vinca, University of Belgrade, Mike Petrovica Alasa 12-14, 11000 Belgrade. Serbia.
authors: Julijana
authors: J
authors: Stanimirovic
authors: Department of Vascular Surgery, Dedinje Cardiovascular Institute, Belgrade University School of Medicine, 11040 Belgrade. Serbia.
authors: Djordje
authors: D
authors: Radak
authors: Institute of Nuclear Sciences Vinca, University of Belgrade, Laboratory of Radiobiology and Molecular Genetics, P.O. Box 522, 11000 Belgrade. Serbia.
authors: Esma R
authors: ER
authors: Isenovic
mesh_terms: D000818:Animals; D059305:Diet, High-Fat; D004958:Estradiol / Q000097:blood*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D047628:Estrogen Receptor alpha; D052002:NF-kappa B p50 Subunit; D004958:Estradiol; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: Cardioprotection; cardiovascular disease; inducible nitric oxide synthase; insulin resistance; obesity; oestradiol