The impact of moderate endurance exercise on cardiac telomeres and cardiovascular remodeling in obese rats

Maria Donatella Semeraro; Antonio Paolo Beltrami; Feras Kharrat; Gunter Almer; Simon Sedej; Wilfried Renner; Hans-Jürgen Gruber; Francesco Curcio; Markus Herrmann

doi:10.3389/fcvm.2022.1080077

The impact of moderate endurance exercise on cardiac telomeres and cardiovascular remodeling in obese rats

Front Cardiovasc Med. 2023 Jan 6:9:1080077. doi: 10.3389/fcvm.2022.1080077. eCollection 2022.

Authors

Affiliations

¹ Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
² Department of Medicine (DAME), University of Udine, Udine, Italy.
³ Department of Cardiology, Medical University of Graz, Graz, Austria.
⁴ BTM BioTechMed-Graz, Graz, Austria.
⁵ Faculty of Medicine, University of Maribor, Maribor, Slovenia.

Abstract

Introduction: Hypercaloric nutrition and physical inactivity cause obesity, a potential driver of myocardial apoptosis and senescence that may accelerate cardiac aging. Although physical activity reduces mortality, its impact on myocardial aging is insufficiently understood. Here we investigated the effects of a hypercaloric high-fat diet (HFD) and regular exercise training on cardiac cells telomeres and histomorphometric indices of cardiac aging.

Methods: Ninety-six 4-months old female Sprague-Dawley rats were fed for 10 months normal (ND) or a HFD diet. Half of the animals in each group performed 30 min treadmill-running sessions on 5 consecutive days per week. At study end, cardiomyocyte cross-sectional area (CSA), interstitial collagen content, vascular density, apoptotic and senescent cells, relative telomere length (RTL), and expression of telomerase-reverse transcriptase (Tert) as marker of telomere-related senescence and apoptosis were analyzed.

Results: Compared to ND, the HFD group developed obesity, higher CSA, lower capillary density and tended to have more apoptotic cardiomyocytes and interstitials cells. Myocardial RTL and the expression of Terf-1 and Terf-2 were comparable in sedentary HFD and ND animals. In the HFD group, regular moderate endurance exercise improved myocardial vascularization, but had no effect on CSA or apoptosis. Notably, the combination of exercise and HFD increased senescence when compared to sedentary ND or HFD, and reduced RTL when compared to exercise ND animals. Exercising HFD animals also showed a trend toward higher Tert expression compared to all other groups. In addition, exercise reduced Terf-1 expression regardless of diet.

Conclusion: HFD-induced obesity showed no effects on myocardial telomeres and induced only mild morphologic alterations. Summarized, long-term moderate endurance exercise partially reverses HFD-induced effects but may even trigger cardiac remodeling in the context of obesity.

Keywords: Sprague-Dawley rats; cardiomyocyte senescence; cardiovascular remodeling; high-fat diet; moderate endurance exercise; shelterin; telomerase; telomere length.

Grants and funding

We would like to acknowledge the financial support of the Friuli Venezia Giulia region through the grant “Lo scompenso cardiaco quale morbo di Alzheimer del cuore. Opportunità diagnostiche e terapeutiche: HEARTzeimer” Bando 2017 per la concessione di contributi per la ricerca operativa clinica, traslazionale, di base, epidemiologica e organizzativa Art. 8, comma 25, L.R. 20/2015.