A practical model of low-volume high-intensity interval training induces mitochondrial biogenesis in human skeletal muscle: potential mechanisms

Abstract

High-intensity interval training (HIT) induces skeletal muscle metabolic and performance adaptations that resemble traditional endurance training despite a low total exercise volume. Most HIT studies have employed 'all out', variable-load exercise interventions (e.g. repeated Wingate tests) that may not be safe, practical and/or well tolerated by certain individuals. Our purpose was to determine the performance, metabolic and molecular adaptations to a more practical model of low-volume HIT. Seven men (21 + or - 0.4 years, V(O2peak) = 46 + or - 2 ml kg(-1) min(-1)) performed six training sessions over 2 weeks. Each session consisted of 8-12 x 60 s intervals at approximately 100% of peak power output elicited during a ramp V(O2) peak test (355 + or - 10 W) separated by 75 s of recovery. Training increased exercise capacity, as assessed by significant improvements on both 50 kJ and 750 kJ cycling time trials (P < 0.05 for both). Skeletal muscle (vastus lateralis) biopsy samples obtained before and after training revealed increased maximal activity of citrate synthase (CS) and cytochrome c oxidase (COX) as well as total protein content of CS, COX subunits II and IV, and the mitochondrial transcription factor A (Tfam) (P < 0.05 for all). Nuclear abundance of peroxisome proliferator-activated receptor gamma co-activator 1alpha (PGC-1alpha) was approximately 25% higher after training (P < 0.05), but total PGC-1alpha protein content remained unchanged. Total SIRT1 content, a proposed activator of PGC-1alpha and mitochondrial biogenesis, was increased by approximately 56% following training (P < 0.05). Training also increased resting muscle glycogen and total GLUT4 protein content (both P < 0.05). This study demonstrates that a practical model of low volume HIT is a potent stimulus for increasing skeletal muscle mitochondrial capacity and improving exercise performance. The results also suggest that increases in SIRT1, nuclear PGC-1alpha, and Tfam may be involved in coordinating mitochondrial adaptations in response to HIT in human skeletal muscle.

Figure 1. Two weeks of high-intensity interval training improves cycling time trial performance

A, time to complete 50 kJ cycling time trial before (pre) and after (post) training. B, time to complete 750 kJ cycling time trial before (pre) and after (post) training. *P < 0.05 vs. pre-training. Values are means ±s.e.m.

Figure 3. High-intensity interval training increases activity and content of the mitochondrial enzyme citrate synthase

A, maximal activity (mmol (kg protein)⁻¹ h⁻¹ w.w.) of citrate synthase (CS) measured in whole muscle homogenates prepared from muscle biopsy samples (v. lateralis) obtained before (pre) and after (post) training. B, protein content of CS before (pre) and after (post) training. *P < 0.05 vs. pre-training. Values are means ±s.e.m. Representative Western blots from two subjects are shown.

Figure 2. High-intensity interval training increases activity and content of the mitochondrial enzyme cytochrome c oxidase

A, maximal activity (mmol (kg protein)⁻¹ h⁻¹ w.w.) of cytochrome c oxidase (COX) measured in whole muscle homogenates prepared from muscle biopsy samples (v. lateralis) obtained before (pre) and after (post) training. B, protein content of COX subunit II before (pre) and after (post) training. C, protein content of COX subunit IV before (pre) and after (post) training. *P < 0.05 vs. pre-training. Values are means ±s.e.m. Representative Western blots from two subjects are shown.

Figure 6. High-intensity interval training increases Tfam protein content

Protein content of mitochondrial transcription factor A (Tfam) measured in whole muscle homogenates prepared from muscle biopsy samples (v. lateralis) obtained before (pre) and after (post) training. *P < 0.05 vs. pre-training. Values are means ±s.e.m. Representative Western blots from two subjects are shown.

Figure 5. High-intensity interval training increases SIRT1 protein content

Protein content of SIRT1 measured in whole muscle homogenates prepared from muscle biopsy samples (v. lateralis) obtained before (pre) and after (post) training. *P < 0.05 vs. pre-training. Values are means ±s.e.m. Representative Western blots from two subjects are shown.

Figure 4. High-intensity interval training increases nuclear but not whole muscle PGC-1α

A, protein content of peroxisome proliferator-activated receptor γ co-activator (PGC)-1α measured in nuclear fractions prepared from muscle biopsy samples (v. lateralis) obtained before (pre) and after (post) training. B, protein content of PGC-1α measured in whole muscle homogenates before (pre) and after (post) training. *P < 0.05 vs. pre-training. Values are means ±s.e.m. PGC-1α antibody specificity is demonstrated in Supplementary Fig. 2. Representative Western blots from two subjects are shown.

Figure 7. High-intensity interval training increases GLUT4 protein content

Protein content of glucose transporter 4 (GLUT4) measured in whole muscle homogenates prepared from muscle biopsy samples (v. lateralis) obtained before (pre) and after (post) training. *P < 0.05 vs. pre-training. Values are means ±s.e.m. Representative Western blots from two subjects are shown.