A diet-induced negative energy balance triggers compensatory mechanisms, e.g., lower metabolic rate and increased appetite. However, knowledge about potential compensatory mechanisms triggered by increased aerobic exercise is limited. A randomized controlled trial was performed in healthy, sedentary, moderately overweight young men to examine the effects of increasing doses of aerobic exercise on body composition, accumulated energy balance, and the degree of compensation. Eighteen participants were randomized to a continuous sedentary control group, 21 to a moderate-exercise (MOD; 300 kcal/day), and 22 to a high-exercise (HIGH; 600 kcal/day) group for 13 wk, corresponding to ϳ30 and 60 min of daily aerobic exercise, respectively. Body weight (MOD: Ϫ3.6 kg, P Ͻ 0.001; HIGH: Ϫ2.7 kg, P ϭ 0.01) and fat mass (MOD: Ϫ4.0 kg, P Ͻ 0.001 and HIGH: Ϫ3.8 kg, P Ͻ 0.001) decreased similarly in both exercise groups. Although the exercise-induced energy expenditure in HIGH was twice that of MOD, the resulting accumulated energy balance, calculated from changes in body composition, was not different (MOD: Ϫ39.6 Mcal, HIGH: Ϫ34.3 Mcal, not significant). Energy balance was 83% more negative than expected in MOD, while it was 20% less negative than expected in HIGH. No statistically significant changes were found in energy intake or nonexercise physical activity that could explain the different compensatory responses associated with 30 vs. 60 min of daily aerobic exercise. In conclusion, a similar body fat loss was obtained regardless of exercise dose. A moderate dose of exercise induced a markedly greater than expected negative energy balance, while a higher dose induced a small but quantifiable degree of compensation.exercise; body weight regulation; compensatory mechanisms; energy balance ALTHOUGH A MODERN SEDENTARY lifestyle along with overeating has been put forward as "Big Two" factors in the etiology of obesity (3,10,29), the outcomes of structured exercise programs designed to promote weight loss are often modest (42,58). This has led to the general (mis)conception that exercise, in itself, is a poor weight management strategy (20,42,49). Apart from a potential lack of compliance, the discrepancy between predicted and observed weight loss is likely due to a combination of physiological and behavioral compensatory changes affecting energy balance. These compensatory changes cause the accumulated energy balance during an exercise intervention to be less negative than would be theoretically predicted from the exercise-induced energy expenditure (ExEE), i.e., the total amount of energy expenditure that is caused by the exercise intervention (12,32,34).Body energy stores are protected against long-term negative energy balance resulting from caloric restriction by a greater than predicted reduction in resting energy expenditure (REE) (28), a decrease in nonexercise activity thermogenesis (NEAT) (40,45), an increase in the metabolic efficiency of physical activity (16,35), and an increase in hedonic (21) and hormonal mediators o...

Physical exercise increases peripheral insulin sensitivity, but regional differences are poorly elucidated in humans. We investigated the effect of aerobic exercise training on insulin-stimulated glucose uptake in five individual femoral muscle groups and four different adipose tissue regions, using dynamic (femoral region) and static (abdominal region) 2-deoxy-2-[ ; mean(SD)], moderately overweight [BMI 28.1(1.8) kg/m 2 ], young [age: 30(6) yr] men were randomized to sedentary living (CON; n ϭ 17 completers) or moderate (MOD; 300 kcal/day, n ϭ 18) or high (HIGH; 600 kcal/day, n ϭ 18) dose physical exercise for 11 wk. At baseline, insulin-stimulated glucose uptake was highest in femoral skeletal muscle followed by intraperitoneal visceral adipose tissue (VAT), retroperitoneal VAT, abdominal (anterior ϩ posterior) subcutaneous adipose tissue (SAT), and femoral SAT (P Ͻ 0.0001 between tissues). Metabolic rate of glucose increased similarly (ϳ30%) in the two exercise groups in femoral skeletal muscle (MOD 24[9,39] , P ϭ 0.003) (mean[95% CI]) and in five individual femoral muscle groups but not in femoral SAT. Standardized uptake value of FDG decreased ϳ24% in anterior abdominal SAT and ϳ20% in posterior abdominal SAT compared with CON but not in either intra-or retroperitoneal VAT. Total adipose tissue mass decreased in both exercise groups, and the decrease was distributed equally among subcutaneous and intra-abdominal depots. In conclusion, aerobic exercise training increases insulin-stimulated glucose uptake in skeletal muscle but not in adipose tissue, which demonstrates some interregional differences. overweight; obesity; metabolism WE HAVE PREVIOUSLY SHOWN that 11 wk of moderate-(ϳ30 min/day) and high-dose (ϳ60 min/day) aerobic physical exercise increases peripheral insulin sensitivity to the same extend in overweight men as measured by the hyperinsulinemicisoglycemic clamp technique (31). However, it was not addressed in which tissues the increase occurred. Skeletal muscle (constituting ϳ40% of body mass) is the major tissue involved in the glucose metabolism and an important site of insulin resistance in obesity and type 2 diabetes (1). Insulin resistance is associated with a reduced percentage of red oxidative skeletal muscle fibers (10), as glucose uptake capacity is larger in red oxidative than in white glycolytic muscle fibers (12,17). Skeletal muscle shows regional heterogeneity metabolically and by distribution of fiber types, with the same tissue at different locations having different metabolic and structural properties (13,23). This metabolic heterogeneity is also found in adipose tissue (8).Physical training is well known to increase insulin-stimulated glucose uptake in the leg as measured by Fick's principle (5, 6). However, this technique does not allow for differentiation between glucose uptake in various tissues of the leg or between individual muscle groups. Uptake of glucose in different tissues can be estimated noninvasively by use of computer tomography (CT) and PET using the glucose anal...

See an invited perspective on this article on page 1776.We prospectively evaluated and compared the diagnostic performance of 99m Tc-hydroxyethylene-diphosphonate ( 99m Tc-HDP) planar bone scintigraphy (pBS), 99m Tc-HDP SPECT/CT, 18 F-NaF PET/CT, and 18 F-NaF PET/MRI for the detection of bone metastases. Methods: One hundred seventeen patients with histologically proven malignancy referred for clinical pBS were prospectively enrolled. pBS and whole-body SPECT/CT were performed followed by 18 F-NaF PET/CT within 9 d. 18 F-NaF PET/MRI was also performed in 46 patients. Results: Bone metastases were confirmed in 16 patients and excluded in 101, which was lower than expected. The number of equivocal scans was significantly higher for pBS than for SPECT/CT and PET/CT (18 vs. 5 and 6, respectively; P 5 0.004 and 0.01, respectively). When equivocal readings were excluded, no statistically significant difference in sensitivity, specificity, positive predictive value, negative predictive value, or overall accuracy were found when comparing the different imaging techniques. In the per-patient analysis, equivocal scans were either assumed positive for metastases ("pessimistic analysis") or assumed negative for metastases ("optimistic analysis"). The percentages of misdiagnosed patients for the pessimistic analysis were 21%, 15%, 9%, and 7% for pBS, SPECT/CT, PET/CT, and PET/MRI, respectively. Corresponding figures for the optimistic analysis were 9%, 12%, 5%, and 7%. In those patients identified as having bone metastases according to the reference standard, SPECT/CT, 18 F-NaF PET/CT, and PET/MRI detected additional lesions compared with pBS in 31%, 63%, and 71%, respectively. Conclusion: 18 F-NaF PET/CT and whole-body SPECT/CT resulted in a significant reduction of equivocal readings compared with pBS, which implies an improved diagnostic confidence. However, the clinical benefit of using, for example, 18 F-NaF PET/CT or PET/MRI as compared with SPECT/CT and pBS in this patient population with a relatively low prevalence of bone metastases (14%) is likely limited. This conclusion is influenced by the low prevalence of patients with osseous metastases. There may well be significant differences in the sensitivity of SPECT/CT, PET/CT, and PET/MRI compared with pBS, but a larger patient population or a patient population with a higher prevalence of bone metastases would have to be studied to demonstrate this.