Spontaneous activity, economy of activity, and resistance to diet-induced obesity in rats bred for high intrinsic aerobic capacity

Abstract

Though obesity is common, some people remain resistant to weight gain even in an obesogenic environment. The propensity to remain lean may be partly associated with high endurance capacity along with high spontaneous physical activity and the energy expenditure of activity, called non-exercise activity thermogenesis (NEAT). Previous studies have shown that highcapacity running rats (HCR) are lean compared to low-capacity runners (LCR), which are susceptible to cardiovascular disease and metabolic syndrome. Here, we examine the effect of diet on spontaneous activity and NEAT, as well as potential mechanisms underlying these traits, in rats selectively bred for high or low intrinsic aerobic endurance capacity. Compared to LCR, HCR were resistant to the sizeable increases in body mass and fat mass induced by a high-fat diet; HCR also had lower levels of circulating leptin. HCR were consistently more active than LCR, and had lower fuel economy of activity, regardless of diet. Nonetheless, both HCR and LCR showed a similar decrease in daily activity levels after high-fat feeding, as well as decreases in hypothalamic orexin-A content. The HCR were more sensitive to the NEAT-activating effects of intraparaventricular orexin-A compared to LCR, especially after high-fat feeding. Lastly, levels of cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) in the skeletal muscle of HCR were consistently higher than LCR, and the high-fat diet decreased skeletal muscle PEPCK-C in both groups of rats. Differences in muscle PEPCK were not secondary to the differing amount of activity. This suggests the possibility that intrinsic differences in physical activity levels may originate at the level of the skeletal muscle, which could alter brain responsiveness to neuropeptides and other factors that regulate spontaneous daily activity and NEAT.

Effects of intrinsic aerobic capacity, aging and voluntary running on skeletal muscle sirtuins and heat shock proteins

“…Taken together, our results are consistent with previous data on rodents 15,25,26 and humans 27,28 , which indicated that genetic predisposition plays a significant role in exercise participation. These results are also consistent with our previous suggestion 14 that genetic pleiotropy may partly explain the associations observed between high physical activity and mortality in our past epidemiological studies, which called for high quality intervention studies to analyse the true effects of physical activity on morbidity and mortality among initially healthy individuals.…”

“…Several large-scale clinical studies have shown that low exercise capacity is the strongest predictor of all-cause mortality [43][44][45]. It has been demonstrated, that in addition to a variety of biochemical and physiological differences, LCRs have significantly shorter lifespan compared to HCRs [26]. Aging is also associated with a decline in the rate of force development, especially during fast contractions [46,47].…”

“…Rats with the highest running capacity from each generation were bred to produce the HCR strain, and rats with the lowest capacity were bred to produce the LCR strain. For the study protocol described here, 79 female rats (39 HCR and 40 LCR) were obtained from generations [23][24][25][26][27]. Each rat was phenotyped for fitness capacity at the University of Michigan (Ann Arbor, Michigan, USA) with a speed-ramped treadmill running test (15° slope, initial velocity of 10 m × min −1 , increased 1 m × min −1 every 2 min), when rats were ~3 months of age.…”

“…Since intrinsic aerobic capacity has pronounced effects in health, complex disease risk and life expectancy [19,22,26] the differences on whole body level of HCR/LCR rats should also be observable in tissue level. In this study the focus is on skeletal muscle.…”

“…We hypothesized that HCRs display higher expression of sirtuin, HSF and Hsp proteins compared to LCRs due to their verified longer median lifespan that is tightly coupled to maximal aerobic capacity and their presumed better capability to compensate aging-related oxidative stress. We also hypothesized that the studied protein levels are higher in HCRs in response to exercise as HCRs have been reported to engage in more voluntary activity on a running wheel and to be spontaneously more active in novel environments than LCRs Novak et al, 2010a;Waters et al, 2008). …”