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. 2014 Jun;46(6):1089-97.
doi: 10.1249/MSS.0000000000000223.

Impact of various exercise modalities on hepatic mitochondrial function

Justin A Fletcher  1 , Grace M Meers, Melissa A Linden, Monica L Kearney, E Matthew Morris, John P Thyfault, R Scott Rector
Affiliations

Impact of various exercise modalities on hepatic mitochondrial function

Justin A Fletcher et al. Med Sci Sports Exerc. 2014 Jun.

Abstract

Purpose: Hepatic mitochondrial adaptations to exercise are largely unknown. In this study, we sought to determine the effects of various exercise modalities on measures of hepatic mitochondrial function and metabolism.

Methods: Male Sprague-Dawley rats were randomly assigned (n = 8-10 per group) into sedentary (SED), voluntary wheel running (VWR), VWR with food pulled during the dark cycle (VMR-OF), treadmill endurance exercise (TM-END; 30 m·min, 12% gradient, 60 min·d, 5 d·wk), or treadmill interval sprint training (TM-IST; 50 m·min, 12% gradient, 6 × 2.5 min bouts, 5 d·wk) groups for a 4-wk intervention.

Results: Hepatic mitochondrial state 3 and maximal uncoupled respiration were significantly (P < 0.05) increased in all four exercise groups compared with SED animals. In addition, hepatic mitochondrial [1-C] pyruvate oxidation to CO2, an index of pyruvate dehydrogenase (PDH) activity, was significantly increased in VWR-OF, TM-END, and TM-IST rats (P < 0.05), whereas exercise-induced increases in [2-C] pyruvate oxidation and [1-C] palmitate oxidation to CO2 did not reach statistical significance. Hepatic mitochondrial sirtuin 3 protein content, which putatively increases activity of mitochondrial proteins, was elevated in the VWR, VWR-OF, and TM-END groups (P < 0.05). In addition, only VWR-OF animals experienced increases in hepatic cytochrome c protein content and phosphoenolpyruvate carboxykinase mRNA, whereas PGC-1α mRNA expression and phospho-CREB protein content was increased in VWR-OF and TM-END groups.

Conclusion: Four weeks of exercise training, regardless of exercise modality, significantly increased hepatic mitochondrial respiration and evoked other unique improvements in mitochondrial metabolism that do not appear to be dependent on increases in mitochondrial content.

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Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Weekly running distance (A) and heart mass to body mass ratio (B). SED, sedentary; VWR, voluntary wheel running; VWR-OF, voluntary wheel running overnight fasted; TM-END, treadmill endurance; TM-IST, treadmill interval sprint training. Values are means ± SE (n= 8-10). Values with different letters are significantly different (P<0.05).
Figure 2
Figure 2
Effects of various exercise modalities on hepatic mitochondrial respiration (A), [1-14C]-pyruvate oxidation to CO2 (B), [2-14C]-pyruvate oxidation to CO2 (C), [1-14C]-palmitate oxidation to CO2 (D), and incomplete [1-14C]-palmitate oxidation (E), in isolated mitochondria. Values are means ± SE (n= 8-10). Values with different letters are significantly different (P<0.05).
Figure 3
Figure 3
Effects of various exercise modalities on hepatic cytochrome c protein content (A), content PGC-1α protein content (B), SIRT1 protein content (C), SIRT3 protein content measured in isolated mitochondria (D) and oxidative phosphorylation (OXPHOS) complex I-V protein content (E). Representative Western blots shown in (F). Values are means ± SE (n= 8-10). Values with different letters are significantly different (P<0.05). AU, arbitrary units; PGC-1α, peroxisome proliferator-activated receptor coactivator-1α.
Figure 4
Figure 4
Effects of various exercise modalities on hepatic cAMP-responsive element-binding protein (CREB) protein content (A), PGC-1α mRNA expression (B), PEPCK mRNA expression (C), and glucose 6 phosphatase mRNA expression (D). Values are means ± SE (n= 8-10). Values with different letters are significantly different (P<0.05).
See this image and copyright information in PMC

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