Effects of 17β-estradiol on cardiac Na+/K+-ATPase in high fat diet fed rats

• Obesity and related disorder such as insulin resistance repress or inactivate Na+/K+-ATPase activity/expression.
• We propose that estradiol-mediated regulation of Na+/K+-ATPase involves IRS-1/PI3K/Akt activation in vivo.
• Estradiol attenuates the detrimental effect of obesity on Na+/K+-ATPase decreasing AT1 receptor and Rho A expression.
• This work will aid the development of new therapeutic strategies for the treatment of heart disease.

The aim of this study was to investigate in vivo effects of estradiol on Na+/K+-ATPase activity/expression in high fat (HF) diet fed rats. Adult male Wistar rats were fed normally (Control, n = 7) or with a HF diet (Obese, n = 14) for 10 weeks. After 10 weeks, half of the obese rats were treated with estradiol (Obese + Estradiol, n = 7, 40 μg/kg, i.p.) as a bolus injection and 24 h after treatment all the rats were sacrificed. Estradiol in vivo in obese rats in comparison with obese non-treated rats led to a statistically significant increase in concentration of serum Na+ (p < 0.05), Na+/K+-ATPase activity (p < 0.01), expression of α1 (p < 0.01) and α2 (p < 0.05) subunit of Na+/K+-ATPase, both PI3K subunits p85 (p < 0.01), p110 (p < 0.05), and association of IRS-1 with p85 (p < 0.05), while significantly decrease expression of AT1 (p < 0.05) and Rho A (p < 0.01) proteins. Our results suggest that estradiol in vivo in pathophysiological conditions, such as obesity accompanied with insulin resistance stimulates activity and expression of Na+/K+-ATPase by a mechanism that involves the participation of IRS-1/PI3K/Akt signaling. In addition, the decreasing level of AT1 and Rho A proteins estradiol probably attenuates the detrimental effect of obesity to decreased IRS-1/PI3K association and consequently reduce Na+/K+-ATPase activity/expression.

Proposed mechanism of in vivo effects of 17β-estradiol on cardiac Na+/K+-ATPase activity and expression in obese rats. Estradiol attenuates the detrimental effects of obesity by downregulation of AT1 and Rho A expression, and by promoting IRS-1 and p85 subunit of PI3K association, resulting in increase of cardiac Na+/K+-ATPase activity and expression in male obese rats. IR – insulin resistance; AT1 – angiotensin II receptor, type 1; Rho A – GTP-binding protein; ROCK – Rho-associated kinase; IRS-1 – insulin receptor substrate 1; PI3K – phosphatidylinositol-3 kinase; Akt – protein kinase B; ↑ – increase; ↓ – decrease.Figure optionsDownload high-quality image (282 K)Download as PowerPoint slide