Beneficial Autophagic Activities, Mitochondrial Function, and Metabolic Phenotype Adaptations Promoted by High-Intensity Interval Training in a Rat Model.

Fang-Hui Li,Timon Cheng-Yi Liu,Rui Duan,Ling Zhu,Jing-Yi Ai,Zhu Min,Lei Sun,Yan-Ying Liu,Tao Li

doi:10.3389/fphys.2018.00571

Abstract

The effects of high-intensity interval (HIIT) and moderate-intensity continuous training (MICT) on basal autophagy and mitochondrial function in cardiac and skeletal muscle and plasma metabolic phenotypes have not been clearly characterized. Here, we investigated how 10-weeks HIIT and MICT differentially modify basal autophagy and mitochondrial markers in cardiac and skeletal muscle and conducted an untargeted metabolomics study with proton nuclear magnetic resonance (1H NMR) spectroscopy and multivariate statistical analysis of plasma metabolic phenotypes. Male Sprague–Dawley rats were separated into three groups: sedentary control (SED), MICT, and HIIT. Rats underwent evaluation of exercise performance, including exercise tolerance and grip strength, and blood lactate levels were measured immediately after an incremental exercise test. Plasma samples were analyzed by 1H NMR. The expression of autophagy and mitochondrial markers and autophagic flux (LC3II/LC3-I ratio) in cardiac, rectus femoris, and soleus muscle were analyzed by western blotting. Time to exhaustion and grip strength increased significantly following HIIT compared with that in both SED and MICT groups. Compared with those in the SED group, blood lactate level, and the expression of SDH, COX-IV, and SIRT3 significantly increased in rectus femoris and soleus muscle of both HIIT and MICT groups. Meanwhile, SDH and COX-IV content of cardiac muscle and COX-IV and SIRT3 content of rectus femoris and soleus muscle increased significantly following HIIT compared with that following MICT. The expression of LC3-II, ATG-3, and Beclin-1 and LC3II/LC3-I ratio were significantly increased only in soleus and cardiac muscle following HIIT. These data indicate that HIIT was more effective for improving physical performance and facilitating cardiac and skeletal muscle adaptations that increase mitochondrial function and basal autophagic activities. Moreover, 1H NMR spectroscopy and multivariate statistical analysis identified 11 metabolites in plasma, among which fine significantly and similarly changed after both HIIT and MICT, while BCAAs isoleucine, leucine, and valine and glutamine were changed only after HIIT. Together, these data indicate distinct differences in specific metabolites and autophagy and mitochondrial markers following HIIT vs. MICT and highlight the value of metabolomic analysis in providing more detailed insight into the metabolic adaptations to exercise training.

Highlights

Emerging human and rodent model research data have shown greater cardiometabolic fitness and insulin sensitivity benefits from high-intensity interval training (HIIT), which is characterized by periods of high-intensity exercise combined with short rest intervals, compared with traditional moderateintensity continuous training (MICT) (MacInnis et al, 2017)
A metabolomics strategy showed that both HIIT and MICT programs promoted an increase in lysine, choline, 3-hydroxybutyrate, and tyrosine, but branch-chained amino acids (BCAAs) and glutamine were upregulated by HIIT when compared with those of the sedentary control (SED) group
10-weeks HIIT and MICT programs did alter the expression of mitochondrial biogenetic markers SDH and COX-IV in the skeletal relative to those in the SED group (Figures 1A,B), which is consistent with the results of significantly greater increases in time to exhaustion as well as lower blood lactate level immediately after the incremental exercise test to exhaustion (Table 2), suggesting that elevated mitochondrial oxidative capacity is involved in improved aerobic capacity following both exercise modalities

Summary

Introduction

Emerging human and rodent model research data have shown greater cardiometabolic fitness and insulin sensitivity benefits from high-intensity interval training (HIIT), which is characterized by periods of high-intensity exercise combined with short rest intervals, compared with traditional moderateintensity continuous training (MICT) (MacInnis et al, 2017). Relatively few studies have investigated specific metabolic adaptations of HIIT or shown that HIIT is superior to MICT, matching total volume. Several studies have applied metabolomics to characterize metabolic signatures of exercise performance (Monleon et al, 2014; Overmyer et al, 2015; Falegan et al, 2017), including robust plasma metabolite profiles associated with moderate changes in the cardiorespiratory fitness status (Chorell et al, 2012) and the enhanced efficiency of fatty acid and branched-chain amino acid (BCAA) utilization in mitochondria (Overmyer et al, 2015).

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