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Chronic β2 -adrenoceptor agonist treatment alters muscle proteome and functional adaptations induced by high intensity training in young men.
Hostrup, M, Onslev, J, Jacobson, GA, Wilson, R, Bangsbo, J
The Journal of physiology. 2018;(2):231-252
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Abstract
KEY POINTS While several studies have investigated the effects of exercise training in human skeletal muscle and the chronic effect of β2 -agonist treatment in rodent muscle, their effects on muscle proteome signature with related functional measures in humans are still incompletely understood. Herein we show that daily β2 -agonist treatment attenuates training-induced enhancements in exercise performance and maximal oxygen consumption, and alters muscle proteome signature and phenotype in trained young men. Daily β2 -agonist treatment abolished several of the training-induced enhancements in muscle oxidative capacity and caused a repression of muscle metabolic pathways; furthermore, β2 -agonist treatment induced a slow-to-fast twitch muscle phenotype transition. The present study indicates that chronic β2 -agonist treatment confounds the positive effect of high intensity training on exercise performance and oxidative capacity, which is of interest for the large proportion of persons using inhaled β2 -agonists on a daily basis, including athletes. ABSTRACT Although the effects of training have been studied for decades, data on muscle proteome signature remodelling induced by high intensity training in relation to functional changes in humans remains incomplete. Likewise, β2 -agonists are frequently used to counteract exercise-induced bronchoconstriction, but the effects β2 -agonist treatment on muscle remodelling and adaptations to training are unknown. In a placebo-controlled parallel study, we randomly assigned 21 trained men to 4 weeks of high intensity training with (HIT+β2 A) or without (HIT) daily inhalation of β2 -agonist (terbutaline, 4 mg dose-1 ). Of 486 proteins identified by mass-spectrometry proteomics of muscle biopsies sampled before and after the intervention, 32 and 85 were changing (false discovery rate (FDR) ≤5%) with the intervention in HIT and HIT+β2 A, respectively. Proteome signature changes were different in HIT and HIT+β2 A (P = 0.005), wherein β2 -agonist caused a repression of 25 proteins in HIT+β2 A compared to HIT, and an upregulation of 7 proteins compared to HIT. β2 -Agonist repressed or even downregulated training-induced enrichment of pathways related to oxidative phosphorylation and glycogen metabolism, but upregulated pathways related to histone trimethylation and the nucleosome. Muscle contractile phenotype changed differently in HIT and HIT+β2 A (P ≤ 0.001), with a fast-to-slow twitch transition in HIT and a slow-to-fast twitch transition in HIT+β2 A. β2 -Agonist attenuated training-induced enhancements in maximal oxygen consumption (P ≤ 0.01) and exercise performance (6.1 vs. 11.6%, P ≤ 0.05) in HIT+β2 A compared to HIT. These findings indicate that daily β2 -agonist treatment attenuates the beneficial effects of high intensity training on exercise performance and oxidative capacity, and causes remodelling of muscle proteome signature towards a fast-twitch phenotype.
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Variants of the peroxisome proliferator-activated receptor gamma- and beta-adrenergic receptor genes are associated with measures of compensatory eating behaviors in young children.
Cecil, JE, Palmer, CN, Fischer, B, Watt, P, Wallis, DJ, Murrie, I, Hetherington, MM
The American journal of clinical nutrition. 2007;(1):167-73
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Abstract
BACKGROUND Young children can regulate energy precisely in the short term, showing the potential for an innate compensation mechanism of eating behavior. However, data suggest that precise compensation is attenuated as a function of increasing adiposity, parental feeding style, and age. Common variation in candidate obesity genes may account for some of the individual variation observed in short-term energy compensation. Polymorphisms in the peroxisome proliferator-activated receptor gamma (PPARG) and beta-adrenergic receptor (ADRB3) genes have been linked to increased body mass index (BMI; in kg/m(2)), obesity, and more recently dietary nutrients and preferences. In addition, common variation in ADRB3 interacts with PPARG to modulate adult body weight. OBJECTIVE This study investigated whether variants in these genes were associated with measurable effects on child eating behavior. DESIGN Children (n=84) aged 4-10 y were prospectively selected for variants of the PPARG locus (Pro12Ala, C1431T). Heights and weights were measured. Energy intake from a test meal was measured 90 min after ingestion of a no-energy (NE), low-energy (LE), or high-energy (HE) preload, and the compensation index (COMPX) was calculated. RESULTS BMI differed significantly by gene model, whereby Pro12Ala was associated with a lower BMI. Poor COMPX was associated with the PPARG T1431 allele (P=0.009). There was a significant interaction between COMPX and the ADRB3 Trp64Arg variant in modulating compensation (P=0.003), whereas the Arg64 allele was associated with good compensation (P=0.001). CONCLUSIONS This is the first study to suggest that a genetic interaction involving ADRB3 and PPARG variants influences eating behavior in children.
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Effects of mind-body therapy on quality of life and neuroendocrine and cellular immune functions in patients with ulcerative colitis.
Elsenbruch, S, Langhorst, J, Popkirowa, K, Müller, T, Luedtke, R, Franken, U, Paul, A, Spahn, G, Michalsen, A, Janssen, OE, et al
Psychotherapy and psychosomatics. 2005;(5):277-87
Abstract
BACKGROUND The aim of this study was to investigate the effects of mind-body therapy on neuroendocrine and cellular immune measures, health-related quality of life and disease activity in patients with ulcerative colitis (UC) in remission. METHODS Thirty UC patients in remission or with low disease activity were randomly assigned to an intervention group (n = 15) or a usual-care waiting control group (n = 15). Intervention consisted of a structured 60-hour training program over 10 weeks which included stress management training, moderate exercise, Mediterranean diet, behavioral techniques and self-care strategies. Quality of life, perceived stress and disease activity were assessed with standardized questionnaires (IBDQ, SF-36, PSS, CAI). In addition, the distribution of circulating lymphocytes and lymphocyte subsets as well as the beta-adrenergic modulation of TNF-alpha production in vitro were analyzed. Urine catecholamines and plasma cortisol, prolactin and growth hormone were measured pre- and postinterventionally, and were compared with a healthy control group (n = 10). RESULTS In response to therapy, patients in the intervention group showed significantly greater improvement in the SF-36 scale Mental Health and the Psychological Health Sum score compared with changes observed in the usual-care waiting control group. Patients in the intervention group showed significantly greater improvement on the IBDQ scale Bowel Symptoms compared with the control group. However, no significant group differences in circulating lymphocyte subsets or endocrine parameters were observed in response to therapy. In addition, no significant effects of intervention on either the basal levels of TNF-alpha or the suppressive action of the beta-adrenergic agonist isoproterenol on TNF-alpha production were observed. CONCLUSION Mind-body therapy may improve quality of life in patients with UC in remission, while no effects of therapy on clinical or physiological parameters were found, which may at least in part be related to selective patient recruitment.
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High spinal anesthesia for cardiac surgery: effects on beta-adrenergic receptor function, stress response, and hemodynamics.
Lee, TW, Grocott, HP, Schwinn, D, Jacobsohn, E, ,
Anesthesiology. 2003;(2):499-510
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Abstract
BACKGROUND This double-blind, randomized, controlled trial examined the effect of high-dose intrathecal bupivacaine in combination with general anesthesia on atrial beta-adrenergic receptor function, the stress response, and hemodynamics during coronary artery bypass graft surgery. METHODS Thirty-eight patients were randomized to either control (n = 19) or intrathecal bupivacaine (ITB) groups (n = 19). Patients in the ITB group received 37.5 mg intrathecal hyperbaric bupivacaine before induction of general anesthesia. Control patients received an injection of local anesthetic into the skin and subcutaneous tissues (sham spinal). Comparisons were made between groups with respect to atrial receptor desensitization and down-regulation, in addition to circulating catecholamines and hemodynamics. RESULTS In patients with cardiopulmonary bypass (CPB) times in excess of 1 h, the ITB group had significantly less atrial beta-receptor dysfunction, as measured by maximal isproteronol, 50% maximal isoproterenol, sodium fluoride-stimulated activity, and zinterol stimulation assays of adenylyl cyclase activity (P < or = 0.02) and beta-adrenergic receptor density (P = 0.02). Serum epinephrine, norepinephrine, and cortisol concentrations were significantly lower in the ITB group, independent of CPB times (P < 0.0001, P < 0.001, and P < 0.05, respectively). ITB patients had a higher cardiac index and a lower pulmonary vascular resistance index in the post-CPB time period (P < 0.01 and P < 0.05, respectively). In the pre-CPB period, mean arterial pressure and systemic vascular resistance index were significantly lower in the ITB group. CONCLUSIONS High-dose intrathecal bupivacaine, when combined with general anesthesia, resulted in less beta-receptor dysfunction and a lower stress response during coronary artery bypass graft surgery.
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The influence of polymorphism at position 16 of the beta2-adrenoceptor on the development of tolerance to beta-agonist.
Taylor, DR, Hancox, RJ, McRae, W, Cowan, JO, Flannery, EM, McLachlan, CR, Herbison, GP
The Journal of asthma : official journal of the Association for the Care of Asthma. 2000;(8):691-700
Abstract
Polymorphism at position 16 of the beta2-adrenoceptor alters receptor down-regulation in vitro. Our aim was to compare the development of tolerance to beta-agonist in homozygous Gly-16 patients with patients harboring the "wild" genotype (homozygous Arg-16) during regular treatment with salmeterol. In a prospective, randomized, double-blind, placebo-controlled, cross-over study, 20 subjects with mild to moderate asthma (10 Gly-16, 10 Arg-16) received 2 weeks of treatment with inhaled salmeterol 100 microg b.i.d. Thereafter, dose responses to inhaled salbutamol were constructed for forced expiratory volume in 1 sec (FEV1), heart rate, QTc interval, serum potassium and glucose, and finger tremor. The protective effect of salbutamol against adenosine monophosphate (AMP) challenge was also measured. Salmeterol resulted in a significant reduction in the area under curve (AUC) for FEV1 (p = 0.01), heart rate (p = 0.01), QTc interval (p = 0.01), and tremor (p = 0.05), and in the maximum responses for FEV1 (p = 0.05), heart rate (p = 0.02), and glucose (p = 0.02). The protective effect of salbutamol against AMP was reduced by 3.61 doubling doses (p < 0.001). However, differences between Gly-16 and Arg-16 patients were small and nonsignificant. Thus, although tolerance is influenced in vitro by polymorphism of the beta2-adrenoceptor, the magnitude of between-genotype differences in vivo is unlikely to be significant.