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Role of GDF15 in active lifestyle induced metabolic adaptations and acute exercise response in mice
(2019)
Physical activity is an important contributor to muscle adaptation and metabolic health. Growth differentiation factor 15 (GDF15) is established as cellular and nutritional stress-induced cytokine but its physiological role in response to active lifestyle or acute exercise is unknown. Here, we investigated the metabolic phenotype and circulating GDF15 levels in lean and obese male C57BI/6J mice with long-term voluntary wheel running (VWR) intervention. Additionally, treadmill running capacity and exercise-induced muscle gene expression was examined in GDF15-ablated mice. Active lifestyle mimic via VWR improved treadmill running performance and, in obese mice, also metabolic phenotype. The post-exercise induction of skeletal muscle transcriptional stress markers was reduced by VWR. Skeletal muscle GDF15 gene expression was very low and only transiently increased post-exercise in sedentary but not in active mice. Plasma GDF15 levels were only marginally affected by chronic or acute exercise. In obese mice, VWR reduced GDF15 gene expression in different tissues but did not reverse elevated plasma GDF15. Genetic ablation of GDF15 had no effect on exercise performance but augmented the post exercise expression of transcriptional exercise stress markers (Atf3, Atf6, and Xbp1s) in skeletal muscle. We conclude that skeletal muscle does not contribute to circulating GDF15 in mice, but muscle GDF15 might play a protective role in the exercise stress response.
Kinetic analysis of the thermic effect of food and its relationship to body composition in humans
(2000)
The course of energy expenditure after a meal can vary widely with regard to the slope of onset, amplitude, and duration of the thermic effect. The aim of the present study was to explore the relationship between the thermic effect of food (TEF), as characterized by kinetic analysis of postprandial energy expenditure, body composition, and variables related to the metabolic syndrome including central obesity, hypertension, and glucose tolerance. A total of 181 men and women (body mass index [BMI] range, 19.4 to 52.2 kg/m2) were characterized for body composition, blood pressure, oral glucose tolerance, and energy expenditure after a test meal. Energy expenditure, as measured by indirect calorimetry, was analyzed over a 6-hour period by 3-parameter curve fitting using equations derived from kinetics describing a biphasic reaction involving 2 consecutive first-order reactions (A->B->C). Apart from total thermic effect of food (TEFk), the curve also provided an estimate of time of peak (Tp) and amplitude of peak (Ap) for each subject. Multiple stepwise regression analysis with TEFk, Ap, and Tp as dependent variables showed significant effects of sex, age, body weight, body fat, -blockade, and body composition on TEF curve parameters. Cluster analysis based on Tp shown 2 distinct clusters with significant differences in age and body fat mass. This study shows that kinetic analysis of postprandial energy expenditure can be used to examine the determinants of the time course of the thermic effect of food in man.