Endurance capacity, not body size, determines physical activity levels: role of skeletal muscle PEPCK

Abstract

Some people remain lean despite pressure to gain weight. Lean people tend to have high daily activity levels, but the source of this increased activity is unknown. We found that leanness cannot be accounted for by increased weight-corrected food intake in two different types of lean rats. As previously reported in lean people, we found that lean rats had higher daily activity levels; lean rats also expended more energy. These lean rats were developed through artificial selection for high aerobic endurance capacity. To test whether our findings extended to a human population, we measured endurance capacity using a VO(2max) treadmill test and daily activity in a group of non-exercising individuals. Similar to lean rats selectively bred for endurance capacity, our study revealed that people with higher VO(2max) also spent more time active throughout the day. Hence, endurance capacity may be the trait that underlies both physical activity levels and leanness. We identified one potential mechanism for the lean, active phenotype in rats, namely high levels of skeletal muscle PEPCK. Therefore, the lean phenotype is characterized by high endurance capacity and high activity and may stem from altered skeletal muscle energetics.

Figure 1. Lean rats do not eat less.

Daily caloric intake, corrected for metabolically-active body mass, was not greater in obese compared to lean rats on a high-fat diet (top). Lean, high-endurance rats consumed more calories after mass correction compared to overweight, low-endurance rats (bottom). *p<0.05

Figure 2. High-endurance rats were more active, regardless of body weight.

Physical activity, in beam breaks/min over 24 hrs (mean±SE), was greater in lean, high-endurance rats compared to overweight, low-endurance rats (A), as was body mass-corrected energy expenditure (B). The same effect was seen in female high- and low-endurance rats, even when body weight did not differ between the two groups (C). Elevations in energy expenditure were seen at the same time as peaks in horizontal physical activity (lean rat shown here; D). *p<0.05.

Figure 3. People with higher endurance had higher daily non-exercise activity.

VO_2max (deviation from predicted VO_2max based on age, sex, and body weight) was significantly positively correlated with time spent standing or walking in healthy human volunteers.

Figure 4. Lean rats have elevated skeletal muscle PEPCK.

Lean, high-endurance rats had higher levels of skeletal muscle PEPCK (A,D) and PEPCK enzymatic activity (B) compared to low-endurance, overweight rats. In rats bred for leanness or obesity on a high-fat diet, heightened skeletal muscle PEPCK was also found in lean compared to obese rats (C, E). *p<0.05.