The effects of long-term moderate exercise and Western-type diet on oxidative/nitrosative stress, serum lipids and cytokines in female Sprague Dawley rats

Maria Donatella Semeraro,Melanie Kaiser,Hans-Jürgen Gruber,Andreas Meinitzer,Gunter Almer,Markus Herrmann,Sieglinde Zelzer,Hubert Scharnagl,Simon Sedej

doi:10.1007/s00394-021-02639-4

Abstract

PurposeRegular exercise reduces obesity and the risk of cardiovascular disease. However, health-promoting benefits of physical activity are commonly associated with increased inflammation and oxidative stress. Here, we tested whether constant moderate exercise is able to prevent or attenuate the oxidative/nitrosative stress, inflammation, and serum lipids in lean and obese rats.MethodsFour-month-old female Sprague Dawley rats received standard or a high-fat diet. Animals were subjected to a physical activity protocol, consisting of 30 min forced treadmill exercise for 5 consecutive days per week during 10 months. Baseline and sedentary (non-exercised) rats were used as controls. Lipids, oxidized low-density lipoprotein cholesterol, nitric oxide metabolites, and pro- and anti-inflammatory markers were measured in blood collected upon euthanasia.ResultsAt variance to young baseline control rats, 14-month-old animals fed normal diet had increased plasma lipid levels, including total cholesterol and triglycerides, which were further elevated in rats that consumed a high-fat diet. While treadmill exercise did not lower the amount of serum lipids in standard diet group, forced physical activity reduced non-high-density lipoprotein cholesterol in response to high-fat diet feeding. Exercised rats fed standard diet or high-fat diet had lower abundancy of nitric oxide metabolites, which coincided with increased levels of oxidized low-density lipoprotein cholesterol. Accordingly, the amount of nitric oxide metabolites correlated inversely with oxidized low-density lipoprotein cholesterol and homo-arginine. Exercise significantly reduced inflammatory cytokines in high-fat diet fed rats only.ConclusionOur study suggests that regular exercise alters the equilibrium between oxidative and anti-oxidative compounds and reduces pro-inflammatory cytokines.

Highlights

Cardiovascular disease (CVD) is a major cause of morbidity and mortality in Western societies and developing countries [1]
It is well established that elevated concentrations of low-density lipoproteins (LDL) cholesterol (LDL-C) promote atherosclerosis and increase the risk of non-fatal and lethal CVD events
The main eNOS uncoupling motifs are the cofactor of nitric oxide (NO) synthesis, tetrahydrobiopterin (BH4), reduced bioavailability of L-arg, or high levels of the endogenous NO synthase (NOS) inhibitor, asymmetrical dimethyl-arginine (ADMA) [8]

Summary

Introduction

Cardiovascular disease (CVD) is a major cause of morbidity and mortality in Western societies and developing countries [1] Modifiable risk factors, such as obesity and sedentarism are highly prevalent in patients with CVD, and both can be improved by safe and effective lifestyle interventions [2]. Elevated oxidative stress characterized by an increased generation of radical oxygen species (ROS) is a common manifestation in patients with CVD, obesity, and diabetes mellitus. These highly reactive compounds can modify many biomarkers including LDL-C [8–10]. The main eNOS uncoupling motifs are the cofactor of NO synthesis, tetrahydrobiopterin (BH4), reduced bioavailability of L-arg, or high levels of the endogenous NOS inhibitor, asymmetrical dimethyl-arginine (ADMA) [8]

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Conclusion