Mechanisms governing the health and performance benefits of exercise

Abstract

Humans are considered among the greatest if not the greatest endurance land animals. Over the last 50 years, as the population has become more sedentary, rates of cardiovascular disease and its associated risk factors such as obesity, type 2 diabetes and hypertension have all increased. Aerobic fitness is considered protective for all-cause mortality, cardiovascular disease, a variety of cancers, joint disease and depression. Here, I will review the emerging mechanisms that underlie the response to exercise, focusing on the major target organ the skeletal muscle system. Understanding the mechanisms of action of exercise will allow us to develop new therapies that mimic the protective actions of exercise.

Keywords: endurance; exercise; insulin-like growth factor; myostatin; nuclear receptors; resistance; skeletal muscle.

Figure 1

Exercise induces changes to skeletal muscle. Exercise induces metabolic and phenotypic changes to skeletal muscle that gives us major health benefits to whole body physiology. Endurance type exercise favours the growth and expression of type I and type IIa (type IIx) muscle fibres, which have increasing oxidative capacity (from type IIx to type I), are mitochondria rich and have an increased blood supply. Resistance exercise favours the growth and hypertrophy of type IIb muscle fibres, which are fast twitch, have increase glycolytic/anaerobic metabolism and produce power/strength over endurance.

Figure 2

Control of endurance exercise muscle phenotype. The increase in oxidative fatty acid metabolic, fatigue resistance muscle fibre generation seen with endurance exercise are mediated by several signalling processes: (i) activation of the master regulator of mitochondrial biosynthesis the PPARγ coactivator-1 (PGC-1α) appears to be a central process. (ii) Several nuclear receptors have also been implicated in the endurance phenotype, which PGC-1α may co-activate, including the PPARα, PPARγ, but in particular PPARβ/δ; the oestrogen-like receptors (ERR)α and ERRγ, and members of the NR4A family, nor-1, nur77 and nur1. (iii) Like resistance exercise, rises in intracellular Ca²⁺ induced with work are also important. (iv) Also controlling the activation of PGC-1α are the activation of the AMP kinase (AMPK), which is activation with an increase in the AMP : ATP ratio, and the deactylase sirtuin (SIRT)-1. (v) Downstream, overexpression of cytosolic phosphoenolpyruvate carboxykinase (PEPCK-c), an enzyme key to central gluconeogenesis, induces an extreme endurance phenotype in mice.