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

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Abstract

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.

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Abbreviations

Akt:

Protein kinase B

CD36:

Cluster of differentiation 36

CVD:

Cardiovascular disease

T2DM:

Type 2 diabetes mellitus

ERα:

Estrogen receptor-α

HF diet:

High-fat diet

HOMA-IR:

HOMA-index of insulin resistance

HOMA-β:

HOMA-index of β-cell function

iNOS:

Inducible nitric oxide synthase

INS:

Insulin

IR:

Insulin resistance

IRS:

Insulin receptor substrate

Na+/K+-ATPase:

Sodium/potassium–adenosine–triphosphatase

PI3K:

Phosphatidylinositol 3-kinase

RhoA:

Ras homolog gene family, member A

ROCK:

Rho kinase

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Acknowledgements

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

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Jovanovic, A., Obradovic, M., Milovanovic, E.S. et al. Changes in cardiac Na+/K+-ATPase expression and activity in female rats fed a high-fat diet. Mol Cell Biochem 436, 49–58 (2017). https://doi.org/10.1007/s11010-017-3077-y

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