17β-Estradiol protects against the effects of a high fat diet on cardiac glucose, lipid and nitric oxide metabolism in rats

•Estradiol treatment influences myocardial glucose and free fatty acid metabolism in rats fed a high fat (HF) diet.•In vivo estradiol treatment impacts on cardiac iNOS expression/activity in HF fed rats.•Estradiol acts via Akt to attenuate the detrimental effects of cardiac iNOS in HF fed rats.

The aim of this study was to investigate the in vivo effects of 17β-estradiol (E2) on myocardial metabolism and inducible nitric oxide synthase (iNOS) expression/activity in obese rats. Male Wistar rats were fed with a normal or a high fat (HF) diet (42% fat) for 10 weeks. Half of the HF fed rats were treated with a single dose of E2 while the other half were placebo-treated. 24 h after treatment animals were sacrificed. E2 reduced cardiac free fatty acid (FFA) (p < 0.05), L-arginine (p < 0.01), iNOS mRNA (p < 0.01), and protein (p < 0.05) levels and translocation of the FFA transporter (CD36) (p < 0.01) to the plasma membrane (PM) in HF fed rats. In contrast, Akt phosphorylation at Thr308 (p < 0.05) and translocation of the glucose transporter GLUT4 (p < 0.05) to the PM increased after E2 treatment in HF rats. Our results indicate that E2 acts via the PI3K/Akt signalling pathway to partially protect myocardial metabolism by attenuating the detrimental effects of increased iNOS expression/activity in HF fed rats.

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