Gavini CK, Mukherjee S, Shukla C, Britton SL, Koch LG, Shi H, Novak CM. Leanness and heightened nonresting energy expenditure: role of skeletal muscle activity thermogenesis. Am J Physiol Endocrinol Metab 306: E635-E647, 2014. First published January 7, 2014; doi:10.1152/ajpendo.00555.2013.-A high-calorie diet accompanied by low levels of physical activity (PA) accounts for the widespread prevalence of obesity today, and yet some people remain lean even in this obesogenic environment. Here, we investigate the cause for this exception. A key trait that predicts high PA in both humans and laboratory rodents is intrinsic aerobic capacity. Rats artificially selected as high-capacity runners (HCR) are lean and consistently more physically active than their low-capacity runner (LCR) counterparts; this applies to both males and females. Here, we demonstrate that HCR show heightened total energy expenditure (TEE) and hypothesize that this is due to higher nonresting energy expenditure (NREE; includes activity EE). After matching for body weight and lean mass, female HCR consistently had heightened nonresting EE, but not resting EE, compared with female LCR. Because of the dominant role of skeletal muscle in nonresting EE, we examined muscle energy use. We found that lean female HCR had higher muscle heat dissipation during activity, explaining their low economy of activity and high activity EE. This may be due to the amplified skeletal muscle expression levels of proteins involved in EE and reduced expression levels of proteins involved in energy conservation in HCR relative to LCR. This is also associated with an increased sympathetic drive to skeletal muscle in HCR compared with LCR. We find little support for the hypothesis that resting metabolic rate is correlated with maximal aerobic capacity if body size and composition are fully considered; rather, the critical factor appears to be activity thermogenesis.nonexercise activity thermogenesis; high-and low-capacity runners; energy expenditure; obesity OBESITY IS INCREASING WORLDWIDE and underlies innumerable associated health problems that lead to decreased quality of life and increased mortality (3,19,20,25,28,75). Although the contribution of diet to the obesogenic environment is unquestioned (69), a sedentary lifestyle also has deleterious effects on body weight (BW) and health (8,15,33). An individual's level of daily physical activity (PA) is a biologically regulated heritable trait that tends to be associated with leanness (31,47,48). We have found that a key feature predicting high PA is intrinsic aerobic capacity; this holds true for both humans and laboratory rodents (35,37,39,56,63,96). Rats that have been selectively bred for high aerobic endurance treadmill running capacity [high-capacity runners (HCR)] are consistently more physically active than their low-endurance counterparts selectively bred as low-capacity runners (LCR). Aerobic capacity is a strong predictor of early morbidity and mortality in both men and women (39, 56); in fact, after age, it is ...