Commentary to Accompany
In the current issue of Exercise and Sport Sciences Reviews, Thyfault and Morris (6) contend, “Although aerobic capacity is linked clearly to health and mortality, it is surprising that so many basic research questions underlying this fundamental physiological readout largely remain unanswered.” Importantly, aerobic capacity is one of the most important predictors of death and chronic diseases. In a 2002 New England Journal of Medicine article, Myers et al. (3) concluded, “Exercise capacity is a more powerful predictor of mortality among men than other established risk factors for cardiovascular disease.” Remarkably, the relative risk of death was 4.5-fold greater in the least aerobic fit group (<6.0 MET), as compared with the most fit group (>13.0 METS). Based on extension to millions of people in each category, this 4.5-fold difference has clinical significance. In addition, as important is quality of life. Nauman et al. (4) performed a second, large study (26,483 subjects) on aerobic capacity, sitting time, and cardiovascular risk factors (factors are defined in their study). Men with the 20th percent lowest aerobic fitness level (<35.7 mL V˙O2peak·kg−1·min−1) and high sitting time (>7 hr·d−1) and women with the lowest fitness level (28.7 mL·kg−1·min−1) and same high sitting time were 28 times and 49 times more likely, respectively, to have a clustering of cardiovascular risk factors as compared with their highest fit groups (defined as men's and women's V˙O2peak > 45.3 and > 35.2 mL·kg−1·min−1, respectively).
Nonalcoholic fatty liver disease is epidemic. Its prevalence in developed countries is 20%–30%, increasing to 70% in obesity and to 90% in diabetics (1). Thus, it should, by definition of epidemic, be considered as an epidemic. In the current article, Thyfault and Morris (6) hypothesized differences in hepatic mitochondrial function in rats with high (HCR) and low (LCR) running capacity, pioneered by Britton and Koch (2), may drive differences in energy expenditure and substrate usage, which contribute to a divergence in susceptibility for obesity and metabolic dysfunction between HCR and LCR. Importantly, the HCR/LCR model permits the study of integrative function in a polygenic manner. Thyfault et al. (5) noted that LCR rats had reduced mitochondrial content and reduced oxidative capacity. In the current article, they conclude that coselection of low aerobic capacity with the primary selector of LCR “causes reduced mitochondrial oxidative capacity that increases susceptibility to both hepatic steatosis and liver injury.” The current article mentions that LCR rats, as compared with HCR, have 1) similar resting energy expenditure; 2) 30% more body weight, due in part to longer body length; 3) lower resting energy expenditure per unit of body mass; 4) lesser spontaneous activity; 5) greater weight when fed a high-fat diet; and 6) lesser metabolic flexibility when placed on a 3-d high-fat diet (increasing whole-body fat usage 15 times less than HCR, which they attribute to LCR's lower intrinsic V˙O2max). The LCR rat is a valuable animal model to study mechanisms connecting low aerobic capacity to higher chronic disease production. In our opinion, future studies linking hepatic mitochondrial function to whole-animal metabolic health should include hepatic PGC-1α. In addition, this article provides intriguing speculation into how the metabolic functions of the liver may influence/associate with aerobic capacity. Regardless of the outcome of the latter future direction, the data continue to pile on for the health importance of high aerobic capacity and the chronic disease and mortality importance of low aerobic capacity.
Frank W. Booth
Department of Biomedical Sciences
Department of Medical Pharmacology and Physiology
Department of Nutrition and Exercise Physiology
and Dalton Cardiovascular Research Center
University of Missouri
Gregory N. RuegseggerDepartment of Biomedical Sciences
University of Missouri
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