Obesity impairs skeletal muscle AMPK signaling during exercise: role of AMPKα2 in the regulation of exercise capacity in vivo.

OBJECTIVE: Skeletal muscle AMP-activated protein kinase (AMPK)α2 activity is impaired in obese, insulin-resistant individuals during exercise. We determined whether this defect contributes to the metabolic dysregulation and reduced exercise capacity observed in the obese state. DESIGN: C57BL/6J wild-type (WT) mice and/or mice expressing a kinase dead AMPKα2 subunit in skeletal muscle (α2-KD) were fed chow or high-fat (HF) diets from 3 to 16 weeks of age. At 15 weeks, mice performed an exercise stress test to determine exercise capacity. In WT mice, muscle glucose uptake and skeletal muscle AMPKα2 activity was assessed in chronically catheterized mice (carotid artery/jugular vein) at 16 weeks. In a separate study, HF-fed WT and α2-KD mice performed 5 weeks of exercise training (from 15 to 20 weeks of age) to test whether AMPKα2 is necessary to restore work tolerance. RESULTS: HF-fed WT mice had reduced exercise tolerance during an exercise stress test, and an attenuation in muscle glucose uptake and AMPKα2 activity during a single bout of exercise (P<0.05 versus chow). In chow-fed α2-KD mice, running speed and time were impaired ∼45 and ∼55%, respectively (P<0.05 versus WT chow); HF feeding further reduced running time ∼25% (P<0.05 versus α2-KD chow). In response to 5 weeks of exercise training, HF-fed WT and α2-KD mice increased maximum running speed ∼35% (P<0.05 versus pre-training) and maintained body weight at pre-training levels, whereas body weight increased in untrained HF WT and α2-KD mice. Exercise training restored running speed to levels seen in healthy, chow-fed mice. CONCLUSION: HF feeding impairs AMPKα2 activity in skeletal muscle during exercise in vivo. Although this defect directly contributes to reduced exercise capacity, findings in HF-fed α2-KD mice show that AMPKα2-independent mechanisms are also involved. Importantly, α2-KD mice on a HF-fed diet adapt to regular exercise by increasing exercise tolerance, demonstrating that this adaptation is independent of skeletal muscle AMPKα2 activity.

Is there a disassociation of maximal oxygen consumption and maximal cardiac output?

PURPOSE: The purpose of the present study was to determine whether maximal cardiac output (Q) is affected by the duration of the maximal exercise test. METHODS: Nine healthy men (N = 6) and women (N = 3) performed three separate maximal treadmill exercise tests, separated by at least 24 h, and underwent a body composition assessment by hydrostatic weighing, all within a 2-wk period. A baseline maximal exercise test was performed to establish VO(2max). The second and third tests, assigned randomly, were designed to elicit the subjects' predetermined VO(2max) in either 6 or 12 min. Heart rate (HR), blood pressure (BP), minutes of ventilation, and oxygen consumption (VO(2)) were measured during all tests. At the end of the 6- and 12-min tests, Q was measured using an acetylene rebreathing technique. Stroke volume (SV), mean arterial pressure (MAP), total peripheral resistance (TPR), and arteriovenous O(2) difference were calculated using standard equations. RESULTS: Repeated-measures ANOVA indicated that there were no significant differences in HR and VO(2max) between the baseline, 6-min, and 12-min tests. Paired t-tests revealed significantly greater Q (25.1 +/- 5.6 vs 23.7 +/- 5.2 L.min-1) and SV (138.3 +/- 31.5 vs 130.5 +/- 31.2 mL) in the 6- versus 12-min tests, respectively. There were no significant differences in systolic BP, diastolic BP, MAP, TPR, or arteriovenous O(2) difference. CONCLUSIONS: Despite there being no difference in VO(2max) between the two tests, the 6-min maximal exercise test resulted in a significantly greater Q than the 12-min test, because of a significantly greater SV. Thus, there was a disassociation between VO(2) and Q during maximal exercise.