Optimizing intramuscular adaptations to aerobic exercise: effects of carbohydrate restriction and protein supplementation on mitochondrial biogenesis

Abstract

Mitochondrial biogenesis is a critical metabolic adaptation to aerobic exercise training that results in enhanced mitochondrial size, content, number, and activity. Recent evidence has shown that dietary manipulation can further enhance mitochondrial adaptations to aerobic exercise training, which may delay skeletal muscle fatigue and enhance exercise performance. Specifically, studies have demonstrated that combining carbohydrate restriction (endogenous and exogenous) with a single bout of aerobic exercise potentiates the beneficial effects of exercise on markers of mitochondrial biogenesis. Additionally, studies have demonstrated that high-quality protein supplementation enhances anabolic skeletal muscle intracellular signaling and mitochondrial protein synthesis following a single bout of aerobic exercise. Mitochondrial biogenesis is stimulated by complex intracellular signaling pathways that appear to be primarily regulated by 5'AMP-activated protein kinase and p38 mitogen-activated protein kinase mediated through proliferator-activated γ receptor co-activator 1 α activation, resulting in increased mitochondrial DNA expression and enhanced skeletal muscle oxidative capacity. However, the mechanisms by which concomitant carbohydrate restriction and dietary protein supplementation modulates mitochondrial adaptations to aerobic exercise training remains unclear. This review summarizes intracellular regulation of mitochondrial biogenesis and the effects of carbohydrate restriction and protein supplementation on mitochondrial adaptations to aerobic exercise.

FIGURE 1

PGC-1α regulation of mitochondrial biogenesis. Aerobic exercise and energy utilization initiate mitochondrial biogenesis. This process is centrally regulated by PGC-1α, which can be activated at the transcriptional level through promoter binding activity and at the post-translational level via direct phosphorylation and deacetylation. PGC-1α controls mitochondrial biogenesis through interaction and coactivation of NRF-1, NRF-2, PPARα, and ERRα, which are regulators of mitochondrial DNA expression, fatty acid β-oxidation, the tricarboxylic acid cycle, and the electron transport chain. Stimulators of mitochondrial biogenesis are shown in green. Inhibitors of mitochondrial biogenesis are depicted in red. AMPK, 5′AMP-activated protein kinase; ATF-2, activating transcription factor 2; CaMK, Ca²⁺/calmodulin-dependent protein kinase; CRE, cAMP response element; CREB, cAMP response element-binding protein; ERRα, estrogen-related receptor α MBP, myelin basic protein; MEF2, myocyte enhancer factor 2; MKK, mitogen-activated protein kinase kinase; mtDNA, mitochondrial DNA; NRF-1/2, nuclear respiratory factor-1/2; p38 MAPK, p38 mitogen-activated protein kinase; PGC-1α, proliferator-activated γ receptor co-activator; SIRT1, silent mating type information regulation 2 homolog 1; TCA, tricarboxylic acid cycle.

FIGURE 2

Integrated muscle protein synthesis and mitochondrial biogenesis intracellular signaling. Muscle protein synthesis and mitochondrial biogenesis require activation of divergent intracellular signaling cascades for initiation; however, individual signaling proteins interact, indicating a convergence between the 2 signaling pathways. Muscle protein synthetic stimulators are depicted in green and inhibitors shown in red. Akt, protein kinase B; AMPK, AMP-activated protein kinase; 4E-BP1, eukaryotic initiation factor 4E-binding protein; eEF2, eukaryotic elongation factor 2; eEF2K, eukaryotic elongation factor 2 kinase; eIF4E/eIF4G, eukaryotic initiation factor; MNK, mitogen and stress activated kinase; mTORC1, mammalian target of rapamycin complex 1; p38 MAPK, p38 mitogen-activated protein kinase; p53, tumor suppressor protein; p70S6K, p70 S6 kinase; PGC-1α, proliferator-activated γ receptor co-activator; Rheb, ras homolog enriched in brain; rpS6, ribosomal protein S6; YY1, yin yang 1; TSC, tuberous sclerosis complex.