Exercise to the rescue

Obesity and the lifestyle factors that fuel it, including poor dietary habits and a sedentary lifestyle, contribute toward the development of cardiovascular disease (CVD), which remains the leading cause of death in the developed world. Perhaps less appreciated as a CVD risk factor, but no less important, is the postprandial (PPL) response to feeding. PPL describes the transient elevation in lipids and circulating triglycerides (TGs) following a meal with moderate to high amounts of dietary fat. The hazards posed by elevated circulating TGs are well documented and include pro-atherogenic effects on the vasculature, unfavourable changes to the lipoprotein profile, and increased risk for thrombosis, among others (Alipour et al. 2008). In the laboratory, human subjects provided a high-fat test meal demonstrate a steady rise in plasma TG, which can reach peak levels approaching 2–3 times basal within 4 h, and remain elevated for up to 8 h post-ingestion. However, in the ‘real world’, things appear even more dire as individuals generally go no longer than a few hours in between meals, thus exposing themselves to repeated elevations in TGs throughout the day. But just when all appears lost, a ‘hero’ has emerged in this story. Indeed, there is an extensive body of literature demonstrating that a prior bout of aerobic exercise can mitigate many of the ‘villains’ brought upon by consuming moderate to excess amounts of dietary fat. These include a significant attenuation in the PPL response following a meal and up-regulation of antioxidant defence systems in the vasculature to protect against potential damage to the endothelium during the postprandial state (Tyldum et al. 2009). In a recent issue of The Journal of Physiology, Jenkins et al. (2011) report for the first time that distinct populations of circulating angiogenic cells (CACs), which play an important role in maintenance and function of the endothelium, come under metabolic duress in response to high-fat feeding, but that these harmful effects can be mostly prevented by a prior bout of aerobic exercise. Specifically, they observed that when recreationally active males, who did not exercise the previous day, were challenged with a high-fat test meal (1362 kcal; 84% fat), two CAC populations, CD31+/CD14−/CD34− and CD31+/CD14+/CD34−, were found to have increased levels of reactive oxygen species (ROS) following the meal. However, a single 50 min bout of stationary cycling at 70% of performed the prior afternoon was sufficient to ‘rescue’ these two CAC populations from these harmful effects of the high-fat meal. In order to gain further insight into how exercise may attenuate ROS generation in these two CAC populations, the authors interrogated multiple enzymes and pathways important in oxidative metabolism, ex vivo. In both CD31+ cell types, they show evidence that the exercise-induced suppression of ROS production may be in part mitochondrial complex I dependent, as rotenone, but not other complex inhibitors, blocked most of the increase in ROS formation observed following the high-fat meal. This was accompanied by an increase in gene expression of the antioxidant enzymes, superoxide dismutase 1 and 2 (SOD1 and SOD2) in CD31+/CD14−/CD34− cells, and reduced storage of neutral lipids in CD31+/CD14+/CD34− cells with prior exercise. It is well known that the endothelium not only plays a critical role in mediating the protective effects associated with exercise, but also serves as a key site for this protection. As noted above, the PPL response to feeding increases circulating TGs, which pose pro-atherogenic effects on the vasculature. Indeed, one of the main causes of atherosclerosis is the development of chronic vascular inflammation as a result of a breach in endothelial integrity. In light of the role that CD31+ angiogenic cells play in maintaining vascular endothelial integrity (Kim et al. 2010), this study has uncovered another potential mechanism whereby acute exercise may reduce the risk of atherosclerosis. These novel observations add to the litany of known benefits associated with a single bout of aerobic exercise, some of which were confirmed in this study, including an attenuated PPL response and reduced plasma endothelial microparticle (EMP) concentrations. However, an important caveat to this story was that CD34+ cells were not ‘rescued’, but were instead adversely affected by the combination of prior exercise and the high-fat meal, as demonstrated by increased ROS production, lower nitric oxide availability and increased storage of neutral lipids during the postprandial state. Therefore, the notion that a single bout of endurance exercise universally spares angiogenic cells from the mayhem invoked by high-fat feeding unfortunately does not appear to be the case. However, it is currently not known how multiple bouts of exercise will affect CD34+ cells, so until studies are conducted to investigate these effects, caution will be needed in moving forward with these results. Given the regularity in which individuals spend in the postprandial state, this study provides a highly relevant context whereby exercise may be an effective remedy to preserve CAC viability and function. This observation could also be of clinical relevance as low CAC levels have been linked to increased cardiovascular risk (Hill et al. 2003) and chronic heart failure (Van Craenenbroeck et al. 2010). Certainly, more work remains to determine the physiological relevance of this exercise-induced protection from ROS to CAC viability as well as the universality of this effect in other CAC populations. Ultimately, this story may prove to be yet another tale of ‘heroics’ by endurance exercise in protecting and maintaining the cardiovascular system.