Jovanovic, Aleksandra (57214859907)Aleksandra (57214859907)JovanovicSudar-Milovanovic, Emina (23570110000)Emina (23570110000)Sudar-MilovanovicObradovic, Milan (48061421600)Milan (48061421600)ObradovicPitt, Samantha J. (7005316383)Samantha J. (7005316383)PittStewart, Alan J. (7403497452)Alan J. (7403497452)StewartZafirovic, Sonja (55697604900)Sonja (55697604900)ZafirovicStanimirovic, Julijana (56441699200)Julijana (56441699200)StanimirovicRadak, Djordje (7004442548)Djordje (7004442548)RadakIsenovic, Esma R. (14040488600)Esma R. (14040488600)Isenovic2025-06-122025-06-122017https://doi.org/10.2174/1570161114666161025101303https://www.scopus.com/inward/record.uri?eid=2-s2.0-85041327847&doi=10.2174%2f1570161114666161025101303&partnerID=40&md5=98696d607a85ffa46ea0623a58835ea7https://remedy.med.bg.ac.rs/handle/123456789/7156Background: 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 ERΚ 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. © 2017 Bentham Science Publishers.CardioprotectionCardiovascular diseaseInducible nitric oxide synthaseInsulin resistanceObesityOestradiol