Molecular Basis of Exercise-Induced Skeletal Muscle Mitochondrial Biogenesis: Historical Advances, Current Knowledge, and Future Challenges.

We provide an overview of groundbreaking studies that laid the foundation for our current understanding of exercise-induced mitochondrial biogenesis and its contribution to human skeletal muscle fitness. We highlight the mechanisms by which skeletal muscle responds to the acute perturbations in cellular energy homeostasis evoked by a single bout of endurance-based exercise and the adaptations resulting from the repeated demands of exercise training that ultimately promote mitochondrial biogenesis through hormetic feedback loops. Despite intense research efforts to elucidate the cellular mechanisms underpinning mitochondrial biogenesis in skeletal muscle, translating this basic knowledge into improved metabolic health at the population level remains a future challenge.

Low carbohydrate, high fat diet impairs exercise economy and negates the performance benefit from intensified training in elite race walkers.

KEY POINTS: Three weeks of intensified training and mild energy deficit in elite race walkers increases peak aerobic capacity independent of dietary support. Adaptation to a ketogenic low carbohydrate, high fat (LCHF) diet markedly increases rates of whole-body fat oxidation during exercise in race walkers over a range of exercise intensities. The increased rates of fat oxidation result in reduced economy (increased oxygen demand for a given speed) at velocities that translate to real-life race performance in elite race walkers. In contrast to training with diets providing chronic or periodised high carbohydrate availability, adaptation to an LCHF diet impairs performance in elite endurance athletes despite a significant improvement in peak aerobic capacity. ABSTRACT: We investigated the effects of adaptation to a ketogenic low carbohydrate (CHO), high fat diet (LCHF) during 3 weeks of intensified training on metabolism and performance of world-class endurance athletes. We controlled three isoenergetic diets in elite race walkers: high CHO availability (g kg-1  day-1 : 8.6 CHO, 2.1 protein, 1.2 fat) consumed before, during and after training (HCHO, n = 9); identical macronutrient intake, periodised within or between days to alternate between low and high CHO availability (PCHO, n = 10); LCHF (< 50 g day-1 CHO; 78% energy as fat; 2.1 g kg-1  day-1 protein; LCHF, n = 10). Post-intervention, V̇O2 peak during race walking increased in all groups (P < 0.001, 90% CI: 2.55, 5.20%). LCHF was associated with markedly increased rates of whole-body fat oxidation, attaining peak rates of 1.57 ± 0.32 g min-1 during 2 h of walking at ∼80% V̇O2 peak . However, LCHF also increased the oxygen (O2 ) cost of race walking at velocities relevant to real-life race performance: O2 uptake (expressed as a percentage of new V̇O2 peak ) at a speed approximating 20 km race pace was reduced in HCHO and PCHO (90% CI: -7.047, -2.55 and -5.18, -0.86, respectively), but was maintained at pre-intervention levels in LCHF. HCHO and PCHO groups improved times for 10 km race walk: 6.6% (90% CI: 4.1, 9.1%) and 5.3% (3.4, 7.2%), with no improvement (-1.6% (-8.5, 5.3%)) for the LCHF group. In contrast to training with diets providing chronic or periodised high-CHO availability, and despite a significant improvement in V̇O2 peak , adaptation to the topical LCHF diet negated performance benefits in elite endurance athletes, in part due to reduced exercise economy.

The erosion of physical activity in Western societies: an economic death march.

By 2030 type 2 diabetes and associated complications will be the seventh leading cause of death globally. In this context, obesity and physical inactivity have emerged as major risk factors for several chronic metabolic disorders. While exercise training exerts numerous health-related benefits in terms of the prevention and treatment of many disease states, including type 2 diabetes, it is currently under-prescribed and under-valued. We contend that unless urgent action is taken to curb the tidal wave of inactivity-related metabolic diseases, the worldwide economic burden associated with the rise in the number of diagnosed cases of type 2 diabetes will trigger the start of an economic death march for both industrial and developing nations alike. In this commentary we look ahead to 2065 and consider the impact that lifestyle interventions and associated strategies are likely to have in curbing the epidemic tide of type 2 diabetes. This is one of a series of commentaries under the banner '50 years forward', giving personal opinions on future perspectives in diabetes, to celebrate the 50th anniversary of Diabetologia (1965-2015).

Exercise and type 2 diabetes: new prescription for an old problem.

During the past 50 years, the prevalence of a cluster of chronic, inactivity-related diseases including obesity, insulin resistance and type 2 diabetes mellitus (T2DM), collectively referred to as 'metabolic syndrome' (MetS) has reached global epidemic proportions. Appropriate exercise training is a clinically proven, cost-effective, primary intervention that delays and in many cases prevents the health burdens associated with MetS. Indeed, there is no single intervention with greater efficacy than physical exercise to reduce the risk of virtually all chronic diseases simultaneously. However compliance to National guidelines for physical activity remains low, with "a lack of time" the most frequently cited barrier to exercise participation by adults, irrespective of age, sex and ethnic background. Part of the growing apathy to modify lifestyle habits is that current public health recommendations may be unrealistic and unattainable for the majority of the populace. Hence, there is an urgent need for innovations in exercise prescription that can be incorporated into daily living and induce clinically beneficial health outcomes. Here we focus attention on a novel form of exercise prescription, high-intensity interval training (HIT), and provide evidence that HIT is a time-efficient and well-tolerated therapeutic intervention to improve cardio-metabolic health in a number of pre-clinical and clinical populations.

Short-term plyometric training improves running economy in highly trained middle and long distance runners.

Fifteen highly trained distance runners VO(2)max 71.1 +/- 6.0 ml.min(-1).kg(-1), mean +/- SD) were randomly assigned to a plyometric training (PLY; n = 7) or control (CON; n = 8) group. In addition to their normal training, the PLY group undertook 3 x 30 minutes PLY sessions per week for 9 weeks. Running economy (RE) was assessed during 3 x 4 minute treadmill runs (14, 16, and 18 km.h(-1)), followed by an incremental test to measure VO(2)max. Muscle power characteristics were assessed on a portable, unidirectional ground reaction force plate. Compared with CON, PLY improved RE at 18 km.h(-1) (4.1%, p = 0.02), but not at 14 or 16 km.h(-1). This was accompanied by trends for increased average power during a 5-jump plyometric test (15%, p = 0.11), a shorter time to reach maximal dynamic strength during a strength quality assessment test (14%, p = 0.09), and a lower VO(2)-speed slope (14%, p = 0.12) after 9 weeks of PLY. There were no significant differences in cardiorespiratory measures or VO(2)max as a result of PLY. In a group of highly-trained distance runners, 9 weeks of PLY improved RE, with likely mechanisms residing in the muscle, or alternatively by improving running mechanics.

Reliability and variability of running economy in elite distance runners.

PURPOSE: To establish the typical error (TE) associated with equipment, testing, and biological variation of a running economy (RE) test in 11 elite male distance runners (VO2max 70.3 +/- 7.3 mL x min(-1) x kg(-1)), and measure the between-athlete variation of 70 highly trained runners (VO2max 69.7 +/- 6.0 mL x min(-1) x kg(-1)) to determine the magnitude of the smallest worthwhile change (SWC) required for RE. METHODS: Runners performed three 4-min bouts of submaximal treadmill running at speeds of 14, 16, and 18 km x h(-1) (0% grade), on two separate occasions within a 7-d period to determine reliability and once over a 3-yr period to measure the SWC. During all RE tests O2 consumption (VO2), ventilation (VE), respiratory exchange ratio (RER), heart rate (HR), stride rate (SR), and concentration of blood lactate (Lac) were determined. RESULTS: The TE for the pooled data of three running speeds (14, 16, and 18 km x h(-1)) was 2.4% for VO2, 7.3% for VE, 27% for Lac, and ranged between 1 and 4% for RER, HR, and SR. CONCLUSIONS: The results demonstrate that although the magnitude of the TE for a submaximal treadmill running protocol of three 4-min work efforts is small (2.4-7.3%) for measures associated with cardiorespiratory parameters, it is three- to fourfold higher for Lac. Given the small TE associated with RE, and a SWC of similar magnitude for this cohort of distance runners, the RE test is useful in detecting changes attributable to training interventions. Changes in RE greater than approximately 2.4% in this cohort of elite distance runners are likely to be "real" and "worthwhile," and not simply related to testing error and typical variation.

Factors affecting running economy in trained distance runners.

Running economy (RE) is typically defined as the energy demand for a given velocity of submaximal running, and is determined by measuring the steady-state consumption of oxygen (VO2) and the respiratory exchange ratio. Taking body mass (BM) into consideration, runners with good RE use less energy and therefore less oxygen than runners with poor RE at the same velocity. There is a strong association between RE and distance running performance, with RE being a better predictor of performance than maximal oxygen uptake (VO2max) in elite runners who have a similar VO2max). RE is traditionally measured by running on a treadmill in standard laboratory conditions, and, although this is not the same as overground running, it gives a good indication of how economical a runner is and how RE changes over time. In order to determine whether changes in RE are real or not, careful standardisation of footwear, time of test and nutritional status are required to limit typical error of measurement. Under controlled conditions, RE is a stable test capable of detecting relatively small changes elicited by training or other interventions. When tracking RE between or within groups it is important to account for BM. As VO2 during submaximal exercise does not, in general, increase linearly with BM, reporting RE with respect to the 0.75 power of BM has been recommended. A number of physiological and biomechanical factors appear to influence RE in highly trained or elite runners. These include metabolic adaptations within the muscle such as increased mitochondria and oxidative enzymes, the ability of the muscles to store and release elastic energy by increasing the stiffness of the muscles, and more efficient mechanics leading to less energy wasted on braking forces and excessive vertical oscillation. Interventions to improve RE are constantly sought after by athletes, coaches and sport scientists. Two interventions that have received recent widespread attention are strength training and altitude training. Strength training allows the muscles to utilise more elastic energy and reduce the amount of energy wasted in braking forces. Altitude exposure enhances discrete metabolic aspects of skeletal muscle, which facilitate more efficient use of oxygen. The importance of RE to successful distance running is well established, and future research should focus on identifying methods to improve RE. Interventions that are easily incorporated into an athlete's training are desirable.