Mads Rosenkilde

Body fat loss and compensatory mechanisms in response to different doses of aerobic exercise—a randomized controlled trial in overweight sedentary males

The amount of weight loss induced by exercise is often disappointing. 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 ∼30 and 60 min of daily aerobic exercise, respectively. Body weight (MOD: -3.6 kg, P < 0.001; HIGH: -2.7 kg, P = 0.01) and fat mass (MOD: -4.0 kg, P < 0.001 and HIGH: -3.8 kg, P < 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: -39.6 Mcal, HIGH: -34.3 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.

Physical Activity Plays an Important Role in Body Weight Regulation

Emerging literature highlights the need to incorporate physical activity into every strategy intended to prevent weight gain as well as to maintain weight loss over time. Furthermore, physical activity should be part of any plan to lose weight. The stimulus of exercise provides valuable metabolic adaptations that improve energy and macronutrient balance regulation. A tight coupling between energy intake and energy expenditure has been documented at high levels of physical exercise, suggesting that exercise may improve appetite control. The regular practice of physical activity has also been reported to reduce the risk of stress-induced weight gain. A more personalized approach is recommended when planning exercise programs in a clinical weight loss setting in order to limit the compensatory changes associated to exercise-induced weight loss. With modern environment promoting overeating and sedentary behavior, there is an urgent need for a concerted action including legislative measures to promote healthy active living in order to curb the current epidemic of chronic diseases.

Distinct expression and ligand-binding profiles of two constitutively active GPR17 splice variants

Background and purpose:  In humans and non‐human primates, the 7TM receptor GPR17 exists in two isoforms differing only by the length of the N‐terminus. Of these, only the short isoform has previously been characterized. Hence, we investigated gene expression and ligand‐binding profiles of both splice variants and furthermore uncovered and characterized constitutive activity of both isoforms.

Structure, function and physiological consequences of virally encoded chemokine seven transmembrane receptors

A number of human and animal herpes viruses encode G‐protein coupled receptors with seven transmembrane (7TM) segments—most of which are clearly related to human chemokine receptors. It appears, that these receptors are used by the virus for immune evasion, cellular transformation, tissue targeting, and possibly for cell entry. In addition, many virally‐encoded chemokine 7TM receptors have been suggested to be causally involved in pathogenic phenotypes like Kaposi sarcoma, atherosclerosis, HIV‐infection and tumour development. The role of these receptors during the viral life cycle and in viral pathogenesis is still poorly understood. Here we focus on the current knowledge of structure, function and trafficking patterns of virally encoded chemokine receptors and further address the putative roles of these receptors in virus survival and host ‐cell and/or ‐immune system modulation. Finally, we highlight the emerging impact of these receptor on virus‐mediated diseases.

Fat oxidation at rest predicts peak fat oxidation during exercise and metabolic phenotype in overweight men

Objective:To elucidate if fat oxidation at rest predicts peak fat oxidation during exercise and/or metabolic phenotype in moderately overweight, sedentary men.Design:Cross-sectional study.Subjects:We measured respiratory exchange ratio (RER) at rest in 44 moderately overweight, normotensive and normoglycemic men and selected 8 subjects with a low RER (L-RER, body mass index (BMI): 27.9±0.9 kg m−2, RER: 0.76±0.02) and 8 with a high RER (H-RER; BMI 28.1±1.1 kg m−2, RER: 0.89±0.02). After an overnight fast, a venous blood sample was obtained and a graded exercise test was performed. Fat oxidation during exercise was quantified using indirect calorimetry.Results:Peak fat oxidation during exercise was higher in L-RER than in H-RER (0.333±0.096 vs 0.169±0.028 g min−1; P<0.01) and occurred at a higher relative intensity (36.2±6.6 vs 28.2±3.1% VO2max, P<0.05). Using the International Diabetes Federation criteria, we found that there was a lower accumulation of metabolic risk factors in L-RER than in H-RER (1.6 vs 3.5, P=0.028), and no subjects in L-RER and four of eight subjects in H-RER had the metabolic syndrome. Resting RER was positively correlated with plasma triglycerides (P<0.01) and negatively with plasma free fatty acids (P<0.05), and peak fat oxidation during exercise was positively correlated with plasma free fatty acid concentration at rest (P<0.05).Conclusion:A low RER at rest predicts a high peak fat oxidation during exercise and a healthy metabolic phenotype in moderately overweight, sedentary men.

Endurance training per se increases metabolic health in young, moderately overweight men.

Health benefits of physical activity may depend on a concomitant weight loss. In a randomized, controlled trial, we compared the effects of endurance training with or without weight loss to the effect of weight loss induced by an energy-reduced diet in 48 sedentary, moderately overweight men who completed a 12-week intervention program of training (T), energy-reduced diet (D), training and increased diet (T-iD), or control (C). An energy deficit of 600 kcal/day was induced by endurance training or diet in T and D and a similar training regimen plus an increased dietary intake of 600 kcal/day defined the T-iD group. Primary end point was insulin sensitivity as evaluated by HOMA-IR (mainly reflecting hepatic insulin sensitivity) and hyperinsulinemic, isoglycemic clamps (primarily reflecting peripheral insulin sensitivity). Body mass decreased in T and D by 5.9 ± 0.7 and 5.3 ± 0.7 kg, respectively, whereas T-iD and C remained weight stable. Total and abdominal fat mass were reduced in an additive manner in the T-iD, D, and T groups by 1.9 ± 0.3/0.2 ± 0.1, 4.4 ± 0.7/0.5 ± 0.1, and 7.7 ± 0.8/0.9 ± 0.1 kg, respectively. HOMA-IR was improved in T, D, and T-iD, whereas insulin-stimulated glucose clearance and suppression of plasma nonesterified fatty acids (NEFAs) were increased only in the two training groups. Thus, loss of fat mass (diet or training induced) improves hepatic insulin sensitivity, whereas peripheral insulin sensitivity in skeletal muscle and adipose tissue is increased by endurance training only. This demonstrates that endurance training per se increases various metabolic health parameters and that endurance training should preferably always be included in any intervention regimen for improving metabolic health in moderately overweight men.

Exercise training favors increased insulin-stimulated glucose uptake in skeletal muscle in contrast to adipose tissue: a randomized study using FDG PET imaging.

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-[¹⁸F]fluoro-d-glucose (FDG) PET/CT methodology during steady-state insulin infusion (40 mU·m⁻²·min⁻¹). Body composition was measured by dual X-ray absorptiometry and MRI. Sixty-one healthy, sedentary [V(O2max) 36(5) ml·kg⁻¹·min⁻¹; mean(SD)], moderately overweight [BMI 28.1(1.8) kg/m²], young [age: 30(6) yr] men were randomized to sedentary living (CON; n = 17 completers) or moderate (MOD; 300 kcal/day, n = 18) or high (HIGH; 600 kcal/day, n = 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 + posterior) subcutaneous adipose tissue (SAT), and femoral SAT (P < 0.0001 between tissues). Metabolic rate of glucose increased similarly (~30%) in the two exercise groups in femoral skeletal muscle (MOD 24[9, 39] μmol·kg⁻¹·min⁻¹, P = 0.004; HIGH 22[9, 35] μmol·kg⁻¹·min⁻¹, P = 0.003) (mean[95% CI]) and in five individual femoral muscle groups but not in femoral SAT. Standardized uptake value of FDG decreased ~24% in anterior abdominal SAT and ~20% 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.

Species‐specific action of (Pro3)GIP – a full agonist at human GIP receptors, but a partial agonist and competitive antagonist at rat and mouse GIP receptors

Specific, high potency receptor antagonists are valuable tools when evaluating animal and human physiology. Within the glucose‐dependent, insulinotropic polypeptide (GIP) system, considerable attention has been given to the presumed GIP receptor antagonist, (Pro3)GIP, and its effect in murine studies. We conducted a pharmacological analysis of this ligand including interspecies differences between the rodent and human GIP system.

Species‐specific action of (Pro3)GIP – an efficacious agonist on human GIP receptor, but partial agonist and competitive antagonist on rat and mouse GIP receptors.

Specific, high potency receptor antagonists are valuable tools when evaluating animal and human physiology. Within the glucose‐dependent, insulinotropic polypeptide (GIP) system, considerable attention has been given to the presumed GIP receptor antagonist, (Pro3)GIP, and its effect in murine studies. We conducted a pharmacological analysis of this ligand including interspecies differences between the rodent and human GIP system.

Only minor additional metabolic health benefits of high as opposed to moderate dose physical exercise in young, moderately overweight men.

The dose–response effects of exercise training on insulin sensitivity, metabolic risk, and quality of life were examined.