Molecular and Cellular Biochemistry

, Volume 436, Issue 1–2, pp 49–58 | Cite as

Changes in cardiac Na+/K+-ATPase expression and activity in female rats fed a high-fat diet

  • Aleksandra Jovanovic
  • Milan Obradovic
  • Emina Sudar Milovanovic
  • Alan J. Stewart
  • Samantha J. Pitt
  • Dragan Alavantic
  • Ema Aleksic
  • Esma R. Isenovic


The aim of this study was to investigate whether the presence of endogenous estradiol alters the effects of a high-fat (HF) diet on activity/expression of the cardiac Na+/K+-ATPase, via PI3K/IRS and RhoA/ROCK signalling cascades in female rats. For this study, female Wistar rats (8 weeks old, 150–200 g) were fed a standard diet or a HF diet (balanced diet for laboratory rats enriched with 42% fat) for 10 weeks. The results show that rats fed a HF diet exhibited a decrease in phosphorylation of the α1 subunit of Na+/K+-ATPase by 30% (p < 0.05), expression of total α1 subunit of Na+/K+-ATPase by 31% (p < 0.05), and association of IRS1 with p85 subunit of PI3K by 42% (p < 0.05), while the levels of cardiac RhoA and ROCK2 were significantly increased by 84% (p < 0.01) and 62% (p < 0.05), respectively. Our results suggest that a HF diet alters cardiac Na+/K+-ATPase expression via molecular mechanisms involving RhoA/ROCK and IRS-1/PI3K signalling in female rats.


High-fat diet Estradiol Na+/K+-ATPase Obesity RhoA/ROCK signalling Female 



Protein kinase B


Cluster of differentiation 36


Cardiovascular disease


Type 2 diabetes mellitus


Estrogen receptor-α

HF diet

High-fat diet


HOMA-index of insulin resistance


HOMA-index of β-cell function


Inducible nitric oxide synthase




Insulin resistance


Insulin receptor substrate




Phosphatidylinositol 3-kinase


Ras homolog gene family, member A


Rho kinase



This work is supported by the Grant Nos. 173033 and III41028 from the Ministry of Science, Republic of Serbia.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.


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© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Laboratory of Radiobiology and Molecular Genetics, Institute of Nuclear Sciences VincaUniversity of BelgradeBelgradeSerbia
  2. 2.School of MedicineUniversity of St AndrewsSt AndrewsUK
  3. 3.Faculty of Dentistry in PancevoUniversity Business AcademyBelgradeSerbia

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