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Influence of a High-Fat Diet on Cardiac iNOS in Female Rats

[ Vol. 15 , Issue. 5 ]

Author(s):

Aleksandra Jovanovic, Emina Sudar-Milovanovic, Milan Obradovic, Samantha J. Pitt, Alan J. Stewart, Sonja Zafirovic, Julijana Stanimirovic, Djordje Radak and Esma R Isenovic   Pages 491 - 500 ( 10 )

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<0.05), 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-κB (NFκB-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.

Results and Conclusion: 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.

Keywords:

Cardioprotection, cardiovascular disease, oestradiol, inducible nitric oxide synthase, insulin resistance, obesity.

Affiliation:

Laboratory of Radiobiology and Molecular Genetics, Institute of Nuclear Sciences Vinca, University of Belgrade, Mike Petrovica Alasa 12-14, 11000 Belgrade, Laboratory of Radiobiology and Molecular Genetics, Institute of Nuclear Sciences Vinca, University of Belgrade, Mike Petrovica Alasa 12-14, 11000 Belgrade, Laboratory of Radiobiology and Molecular Genetics, Institute of Nuclear Sciences Vinca, University of Belgrade, Mike Petrovica Alasa 12-14, 11000 Belgrade, School of Medicine, University of St Andrews, St Andrews, KY16 9TF, School of Medicine, University of St Andrews, St Andrews, KY16 9TF, Laboratory of Radiobiology and Molecular Genetics, Institute of Nuclear Sciences Vinca, University of Belgrade, Mike Petrovica Alasa 12-14, 11000 Belgrade, Laboratory of Radiobiology and Molecular Genetics, Institute of Nuclear Sciences Vinca, University of Belgrade, Mike Petrovica Alasa 12-14, 11000 Belgrade, Department of Vascular Surgery, Dedinje Cardiovascular Institute, Belgrade University School of Medicine, 11040 Belgrade, Institute of Nuclear Sciences Vinca, University of Belgrade, Laboratory of Radiobiology and Molecular Genetics, P.O. Box 522, 11000 Belgrade

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