Changes in the urinary metabolome accompanied alterations in body mass and composition in women with overweight - impact of high versus low protein breakfast.

INTRODUCTION: Understanding why subjects with overweight and with obesity vary in their response to dietary interventions is of major interest for developing personalized strategies for body mass regulation. OBJECTIVES: The aim of this study was to investigate the relationship between changes in the urine metabolome and body mass during a breakfast meal intervention. Furthermore, we aimed to elucidate if the baseline urine metabolome could predict the response to the two types of breakfast meals (high versus low protein) during the intervention. METHODS: A total of 75 young, women with overweight were randomly allocated to one of two intervention groups: (1) High-protein (HP) or (2) low-protein (LP) breakfast as part of their habitual diet during a 12-week intervention. Beside the breakfast meal, participants were instructed to eat their habitual diet and maintain their habitual physical activity level. Nuclear magnetic resonance-based metabolomics was conducted on urine samples collected at baseline (wk 0), mid-intervention (wk 6), and at endpoint (wk 12). At baseline and endpoint, body mass was measured and DXA was used to measure lean body mass and fat mass. RESULTS: The baseline urine metabolite profile showed a slightly higher correlation (R2 = 0.56) to body mass in comparison with lean body mass (R2 = 0.51) and fat mass (R2 = 0.53). Baseline 24-h urinary excretion of trigonelline (p = 0.04), N, N-dimethylglycine (p = 0.02), and trimethylamine (p = 0.03) were significantly higher in individuals who responded with a reduction in body mass to the HP breakfast. CONCLUSIONS: Differences in the urine metabolome were seen for women that obtained a body weight loss in the response to the HP breakfast intervention and women who did not obtain a body weight loss, indicating that the urine metabolome contains information about the metabolic phenotype that influences the responsiveness to dietary interventions.

Effects of transdermal estrogen therapy on satellite cell number and molecular markers for muscle hypertrophy in response to resistance training in early postmenopausal women.

PURPOSE: To investigate the effects of resistance training with or without transdermal estrogen therapy (ET) on satellite cell (SC) number and molecular markers for muscle hypertrophy in early postmenopausal women. METHODS: Using a double-blinded randomized controlled design, we allocated healthy, untrained postmenopausal women to perform 12 weeks of resistance training with placebo (PLC, n = 16) or ET (n = 15). Muscle biopsies obtained before and after the intervention, and two hours after the last training session were analyzed for fiber type, SC number and molecular markers for muscle hypertrophy and degradation (real-time PCR, western blotting). RESULTS: The analysis of SCs per Type I fiber showed a time x treatment interaction caused by a 47% decrease in PLC, and a 26% increase after ET after the training period. Also, SCs per Type II fiber area was lower after the intervention driven by a 57% decrease in PLC. Most molecular markers changed similarly in the two groups. CONCLUSION: A decline in SC per muscle fiber was observed after the 12-week training period in postmenopausal women, which was counteracted when combined with use of transdermal ET. CLINICAL TRIAL REGISTRATION NUMBER: nct03020953.

Muscle Performance during the Menstrual Cycle Correlates with Psychological Well-Being, but Not Fluctuations in Sex Hormones.

PURPOSE: We aimed to study variations in strength and power performance during the menstrual cycle (MC) in eumenorrheic young women and during the pill cycle in oral contraceptives (OC) users. METHODS: Forty healthy, normal-weight women between 18 and 35 yr (n = 30 eumenorrheic women; n = 10 OC users) completed this prospective cohort study. Seven to nine times during the MC/pill-cycle, the participants completed a physical performance test series, a questionnaire about psychological well-being, blood sampling, and determination of body mass. The physical tests included isometric handgrip strength, elbow flexor strength, countermovement jump (CMJ) height, and a 10-s Wingate bike test. RESULTS: No direct correlation was observed between the variations in sex hormones and physical performance parameters. However, positive correlations were observed between physical performance outcomes and self-reported motivation, perception of own physical performance level, pleasure level, and arousal level. CMJ was 6% lower in the late luteal phase (LL) compared with the midluteal phase (ML) (P = 0.04). Wingate peak power was 3% lower in early follicular (EF) compared with the ML (P = 0.04). Furthermore, Wingate average power was 2%-5% lower in LL compared with all other MC phases. In line with these observations, physical pain was higher in EF and LL, and the pleasure level was lower in EF compared with the other MC phases. In OC users, we observed no variation in performance and self-reported parameters between the placebo-pill phase and the OC-pill phase. CONCLUSIONS: Impairments in CMJ and Wingate performance were observed at the end and start of MC compared with other MC phases, which were associated with lower psychological well-being, but not the sex hormone fluctuations.

Sex Hormones and Satellite Cell Regulation in Women.

Recent years have seen growing scholarly interest in female physiology in general. Moreover, particular attention has been devoted to how concentrations of female sex hormones vary during the menstrual cycle and menopausal transition and how hormonal contraception and hormonal therapy influence skeletal muscle tissue. While much effort has been paid to macro outcomes, such as muscle function or mass, rather less attention has been paid to mechanistic work that may help explain the underlying mechanism through which sex hormones regulate skeletal muscle tissue. Evidence from animal studies shows a strong relationship between the female sex hormone estrogen and satellite cells (SCs), a population of muscle stem cells involved in skeletal muscle regulation. A few human studies investigating this relationship have been published only recently. Thus, the purpose of this study was to bring an updated review on female sex hormones and their role in SC regulation. First, we describe how SCs regulate skeletal muscle maintenance and repair and introduce sex hormone signaling within the muscle. Second, we present evidence from animal studies elucidating how estrogen deficiency and supplementation influence SCs. Third, we present results from investigations from human trials including women whose concentrations of female hormones differ due to menopause, hormone therapy, hormonal contraceptives, and the menstrual cycle. Finally, we discuss research and methodological recommendations for future studies aiming at elucidating the link between female sex hormones and SCs with respect to aging and training.

Estrogen modulates metabolic risk profile after resistance training in early postmenopausal women: a randomized controlled trial.

OBJECTIVE: Women experience an unhealthy change in metabolic risk profile at menopause. The purpose of the present study was to determine effects of resistance training with or without transdermal estrogen therapy (ET) on adipose tissue mass and metabolic risk profile in early postmenopausal women. METHODS: A double-blinded randomized controlled trial, where healthy, untrained postmenopausal women were allocated to supervised resistance training with placebo (PLC, n = 16) or transdermal ET (n = 15) for 12 weeks. Endpoints with prespecified hypotheses were the change in total fat mass (FM) (main endpoint) and the change in visceral FM (secondary endpoint) from before to after the intervention. Additionally, prespecified endpoints of body composition, metabolic health-related blood markers, fat%, fat cell size, and lipogenic markers in subcutaneous adipose tissue (SAT) from abdominal and femoral region were explored. RESULTS: Compared with the ET group, the PLC group experienced a greater reduction (time × treatment interaction P < 0.05) in total FM (PLC vs ET: -5.6% vs -1.1%) and visceral FM (-18.6% vs -6.8%), and femoral SAT (-5.6% vs 1.0%), but not abdominal SAT mass (-8.5% vs -2.8%, P = 0.15).The ET group improved their metabolic blood profile by reduced low-density lipoprotein, glucose and hemoglobin A1c compared with PLC (time × treatment interaction P < 0.05). The intervention induced changes in lipolytic markers of abdominal SAT, whereas no changes were detected in femoral SAT. CONCLUSION: Use of transdermal ET reduced adipose tissue loss, but improved metabolic blood markers when combined with 12 weeks of progressive resistance training in early postmenopausal women.

Influence of Fermented Red Clover Extract on Skeletal Muscle in Early Postmenopausal Women: A Double-Blinded Cross-Over Study.

Objective: To investigate effects of supplementation with a fermented red clover (RC) extract on signaling proteins related to muscle protein synthesis and breakdown at rest and in response to a resistance exercise bout. Methods: Ten postmenopausal women completed a double-blinded cross-over trial with two different intervention periods performed in random order: (A) RC extract twice daily for 14 days, and (B) placebo drink twice daily for 14 days. The intervention periods were separated by a two-week washout period. After each intervention period a muscle tissue sample was obtained before and three hours after a one-legged resistance exercise bout. Muscle strength was assessed before and after each intervention period. Results: Protein expression of FOXO1 and FOXO3a, two key transcription factors involved in protein degradation, were significantly lower and HSP27, a protein involved in cell protection and prevention of protein aggregation was significantly higher following RC extract compared to placebo. No significant treatment × time interaction was observed for muscle protein expression in response to exercise. However, p-mTOR, p-p70S6k and HSP90 protein content were significantly increased in response to exercise in both groups. Conclusions: This study demonstrates that RC extract supplementation downregulates molecular markers of muscle protein degradation compared to placebo in postmenopausal women.

Molecular markers of skeletal muscle hypertrophy following 10 wk of resistance training in oral contraceptive users and nonusers.

The objective was to determine whether skeletal muscle molecular markers and SC number were influenced differently in users and nonusers of oral contraceptives (OCs) following 10 wk of resistance training. Thirty-eight young healthy untrained users (n = 20) and nonusers of OC (n = 18) completed a 10-wk supervised progressive resistance training program. Before and after the intervention, a muscle tissue sample was obtained from the vastus lateralis muscle for analysis of muscle fiber cross-sectional area (fCSA) and satellite cell (SC) and myonuclei number using immunohistochemistry, gene expression using PCR, protein expression, and myosin heavy chain composition. Following the training period, quadriceps fCSA (P < 0.05), SCs/type I fiber (P = 0.05), and MURF-1 mRNA (P < 0.01) were significantly increased with no difference between the groups. However, SCs/total fiber and SCs/type II fiber increased in OC users only, and SCs/type II fCSA tended (P = 0.055) to be greater in the OC users. Furthermore, in OC users there were a fiber type shift from myosin heavy chain (MHC) IIx to MHC IIa (P < 0.01), and expression of muscle regulatory factor 4 (MRF4) mRNA (P < 0.001) was significantly greater than in non-OC users. Use of second-generation OCs in young untrained women increased skeletal muscle MRF4 expression and SC number following 10 wk of resistance training compared with nonusers.NEW & NOTEWORTHY The effect of oral contraceptive use on the skeletal muscle regulatory pathways in response to resistance training has not been investigated previously. Here we present novel data, demonstrating that use of second-generation oral contraceptives in young untrained women increased skeletal muscle regulatory factor 4 expression and satellite cell number following 10 wk of resistance training compared with nonusers.

Transdermal Estrogen Therapy Improves Gains in Skeletal Muscle Mass After 12 Weeks of Resistance Training in Early Postmenopausal Women.

CONTEXT: Women show an accelerated loss of muscle mass around menopause, possibly related to the decline in estrogen. Furthermore, the anabolic response to resistance exercise seems to be hampered in postmenopausal women. OBJECTIVE: We aimed to test the hypothesis that transdermal estrogen therapy (ET) amplifies the skeletal muscle response to resistance training in early postmenopausal women. DESIGN: A double-blinded randomized controlled study. SETTING: Department of Public Health, Aarhus University, Denmark. PARTICIPANTS: Thirty-one healthy, untrained postmenopausal women no more than 5 years past menopause. INTERVENTIONS: Supervised resistance training with placebo (PLC, n = 16) or transdermal ET (n = 15) for 12 weeks. MAIN OUTCOME MEASURES: The primary outcome parameter was a cross-sectional area of quadriceps femoris measured by magnetic resonance imaging, and secondary parameters were fat-free mass (dual-energy X-ray absorptiometry), muscle strength, and functional tests. RESULTS: The increase in muscle cross-sectional area was significantly greater in the ET group (7.9%) compared with the PLC group (3.9%) (p < 0.05). Similarly, the increase in whole-body fat-free mass was greater in the ET group (5.5%) than in the PLC group (2.9%) (p < 0.05). Handgrip strength increased in ET (p < 0.05) but did not change in the PLC group. Muscle strength parameters, jumping height, and finger strength were all improved after the training period with no difference between groups. CONCLUSION: The use of transdermal ET enhanced the increase in muscle mass in response to 12 weeks of progressive resistance training in early postmenopausal women.