Utilizing small nutrient compounds as enhancers of exercise-induced mitochondrial biogenesis.

Daniel M Craig,Micah Y Belew,Kevin Currell,Andrew Philp,Keith Baar,Ben Stocks,Stephen P Ashcroft

doi:10.3389/fphys.2015.00296

Abstract

Endurance exercise, when performed regularly as part of a training program, leads to increases in whole-body and skeletal muscle-specific oxidative capacity. At the cellular level, this adaptive response is manifested by an increased number of oxidative fibers (Type I and IIA myosin heavy chain), an increase in capillarity and an increase in mitochondrial biogenesis. The increase in mitochondrial biogenesis (increased volume and functional capacity) is fundamentally important as it leads to greater rates of oxidative phosphorylation and an improved capacity to utilize fatty acids during sub-maximal exercise. Given the importance of mitochondrial biogenesis for skeletal muscle performance, considerable attention has been given to understanding the molecular cues stimulated by endurance exercise that culminate in this adaptive response. In turn, this research has led to the identification of pharmaceutical compounds and small nutritional bioactive ingredients that appear able to amplify exercise-responsive signaling pathways in skeletal muscle. The aim of this review is to discuss these purported exercise mimetics and bioactive ingredients in the context of mitochondrial biogenesis in skeletal muscle. We will examine proposed modes of action, discuss evidence of application in skeletal muscle in vivo and finally comment on the feasibility of such approaches to support endurance-training applications in humans.

Highlights

Endurance training leads to increased rates of fat oxidation and glycogen synthesis in skeletal muscle, which in turn contributes to enhanced endurance performance (Achten and Jeukendrup, 2004)
It is the cumulative effect of these signaling cascades that result in long term adaptations in skeletal muscle including the increased abundance of proteins involved in mitochondrial adenosine triphosphate (ATP) production, the tricarboxylic acid (TCA) cycle and the transport and oxidation of fatty acids
These results suggest that (−)-epicatechin supplementation independently resulted in a response similar to endurance exercise as well as augmented the endurance exercise training response, epicatechin has the potential to promote metabolic changes within skeletal muscle resulting in mitochondrial biogenesis

Summary

INTRODUCTION

Endurance training leads to increased rates of fat oxidation and glycogen synthesis in skeletal muscle, which in turn contributes to enhanced endurance performance (Achten and Jeukendrup, 2004). Nutritional and training strategies aimed to maximize these adaptive responses have been an area of intense investigation. Even though traditional nutritional supplementation strategies were primarily aimed at prolonging endurance performance (Maughan, 2002), increased understanding of the molecular regulation of skeletal muscle adaptation during, and in response to exercise, have led to contemporary approaches utilizing pharmacological compounds, functional foods, or small naturally occurring bioactive ingredients to substitute for, or augment the training response. The aim of this review is to (1) discuss the benefits of regular exercise training on whole body and skeletal muscle-specific adaptation, (2) introduce the concept of exercise mimetics and. Nutritional activators of mitochondrial biogenesis discuss their feasibility in skeletal muscle in vivo, (3) critique the literature detailing the use of small nutritional bioactive ingredients as modulators of mitochondrial function in skeletal muscle in vitro and in vivo, and (4) discuss the efficacy of each approach for use in humans

ENDURANCE EXERCISE AND AEROBIC ADAPTATIONS

MOLECULAR REGULATION OF SKELETAL MUSCLE MITOCHONDRIAL BIOGENESIS

THE SCIENTIFIC BASIS OF EXERCISE MIMETICS

Amino Acids

Findings

CONCLUSIONS