Peak fat oxidation, peak oxygen uptake, and running performance increase during pre-season in sub-elite male football players.

PURPOSE: In Football, the high-intensity running bouts during matches are considered decisive. Interestingly, recent studies showed that peak fat oxidation rates (PFO) are higher in football players than other athletes. This study aimed to investigate whether PFO increases following a pre-season. Secondarily, and due to COVID-19, we investigated whether PFO is related to the physical performance in a subgroup of semi-professional male football players. METHODS: Before and after 8 weeks of pre-season training, 42 sub-elite male football players (18 semi-professionals and 24 non-professionals) had a dual-energy x-ray absorptiometry scan and performed a graded exercise test on a treadmill for the determination of PFO, the exercise intensity eliciting PFO (Fatmax) and peak oxygen uptake (V̇O2peak). Additionally, the semi-professional players performed a Yo-Yo Intermittent Recovery Test level 2 (YYIR2) before and after pre-season training to determine football-specific running performance. RESULTS: PFO increased by 11 ± 10% (mean ± 95% CI), p = 0.031, and V̇O2peak increased by 5 ± 1%, p < 0.001, whereas Fatmax was unchanged (+12 ± 9%, p = 0.057), following pre-season training. PFO increments were not associated with increments in V̇O2peak (Pearson's r2 = 0.00, p = 0.948) or fat-free mass (FFM) (r2 = 0.00, p = 0.969). Concomitantly, YYIR2 performance increased in the semi-professional players by 39 ± 17%, p < 0.001, which was associated with changes in V̇O2peak (r2 = 0.35, p = 0.034) but not PFO (r2 = 0.13, p = 0.244). CONCLUSIONS: PFO, V̇O2peak, and FFM increased following pre-season training in sub-elite football players. However, in a subgroup of semi-professional players, increments in PFO were not associated with improvements in YYIR2 performance nor with increments in V̇O2peak and FFM.

Effect of repeated prolonged exercise on liver fat content and visceral adipose tissue in well-trained older men.

INTRODUCTION: Liver fat (LF) and visceral adipose tissue (VAT) content decreases with training, however, this has mainly been investigated in sedentary obese or healthy participants. The aim of this study was to investigate the effects of repeated prolonged exercise on LF and VAT content in well-trained older men and to compare baseline LF and VAT content to recreationally active older men. METHOD: A group of five well-trained older men were tested before and after cycling a total distance of 2558 km in 16 consecutive days. VAT content and body composition was measured using DXA before a bicycle ergometer test was performed to determine maximal fat oxidation (MFO), maximal oxygen consumption ( VO 2 max $$ {\mathrm{VO}}_{2_{\mathrm{max}}} $$ ), and the relative intensity at which MFO occurred (Fatmax). LF content was measured on a separate day using MRI. For comparison of baseline values, a control group of eight healthy age- and BMI-matched recreationally active men were recruited. RESULTS: The well-trained older men had lower VAT (p = 0.02), and a tendency toward lower LF content (p = 0.06) compared with the control group. The intervention resulted in decreased LF content (p = 0.02), but VAT, fat mass, and lean mass remained unchanged. VO 2 max $$ {\mathrm{VO}}_{2_{\mathrm{max}}} $$ , MFO, and Fatmax were not affected by the intervention. CONCLUSION: The study found that repeated prolonged exercise reduced LF content, but VAT and VO 2 max $$ {\mathrm{VO}}_{2_{\mathrm{max}}} $$ remained unchanged. Aerobic capacity was aligned with lower LF and VAT in older active men.

Cross-species comparison of pregnancy-induced GDF15.

Growth differentiation factor 15 (GDF15) is a stress-induced cytokine. Although the exact physiological function of GDF15 is not yet fully comprehended, the significant elevation of circulating GDF15 levels during gestation suggests a potential role for this hormone in pregnancy. This is corroborated by genetic association studies in which GDF15 and the GDF15 receptor, GDNF family receptor alpha like (GFRAL) have been linked to morning sickness and hyperemesis gravidarum (HG) in humans. Here, we studied GDF15 biology during pregnancy in mice, rats, macaques, and humans. In contrast to macaques and humans, mice and rats exhibited an underwhelming induction in plasma GDF15 levels in response to pregnancy (∼75-fold increase in macaques vs. ∼2-fold increase in rodents). The changes in circulating GDF15 levels were corroborated by the magnitude of Gdf15 mRNA and GDF15 protein expression in placentae from mice, rats, and macaques. These species-specific findings may help guide future studies focusing on GDF15 in pregnancy and on the evaluation of pharmacological strategies to interfere with GDF15-GFRAL signaling to treat severe nausea and HG.NEW & NOTEWORTHY In the present study pregnancy-induced changes in circulating growth differentiation factor 15 (GDF15) in rodents, rhesus macaques, and humans are mapped. In sum, it is demonstrated that humans and macaques exhibit a tremendous increase in placental and circulating GDF15 during pregnancy. In contrast, GDF15 is negligibly increased in pregnant mice and rats, questioning a physiological role for GDF15 in pregnancy in rodents.

The effect of 8 weeks of physical training on muscle performance and maximal fat oxidation rates in patients treated with simvastatin and coenzyme Q10 supplementation.

Statins are prescribed for the treatment of elevated cholesterol, but they may negatively affect metabolism, muscle performance, and the response to training. Coenzyme Q10 (CoQ10) supplementation may alleviate these effects. Combined simvastatin and CoQ10 treatment during physical training has never been tested. We studied the response to 8 weeks training (maximal oxygen uptake ( V̇O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$ ), fat oxidation (MFO), the workload at which MFO occurred, and muscle strength) in statin naive dyslipidaemic patients who received simvastatin (40 mg/day) with (S + Q, n = 9) or without (S + Pl, n = 10) CoQ10 supplementation (2 × 200 mg/day) or placebo (Pl + Pl, n = 7) in a randomized, double-blind placebo-controlled study. V̇O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$ and maximal workload increased with training (main effect of time, P < 0.05). MFO increased from 0.29 ± 0.10, 0.26 ± 0.10, and 0.38 ± 0.09 to 0.42 ± 0.09, 0.38 ± 0.10 and 0.48 ± 0.16 g/min in S + Q, S + Pl, and Pl + Pl, respectively (main effect of time, P = 0.0013). The workload at MFO increased from 75 ± 25, 56 ± 23, and 72 ± 17 to 106 ± 25, 84 ± 13 and 102 ± 31 W in S + Q, S + Pl, and Pl + Pl, respectively (main effect of time, P < 0.0001). Maximal voluntary contraction and rate of force development were unchanged. Exercise improved aerobic physical capacity and simvastatin with or without CoQ10 supplementation did not inhibit this adaptation. The similar increases in MFO and in the workload at which MFO occurred in response to training shows that the ability to adapt substrate selection and oxidation rates is preserved with simvastatin treatment, despite the potential negative impact of simvastatin at the mitochondrial level. CoQ10 supplementation does not augment this adaptation. KEY POINTS: Simvastatins are prescribed for treatment of elevated cholesterol, but they may negatively affect metabolism, muscle performance and the response to training. Coenzyme Q10 (CoQ10) supplementation may alleviate some of these effects. We found that simvastatin treatment does not negatively affect training-induced adaptations of substrate oxidation during exercise. Likewise, maximal oxygen uptake increases with physical training also in patients in treatment with simvastatin. CoQ10 supplementation in simvastatin-treated patients presents no advantage in the adaptations to physical training Simvastatin treatment decreases plasma concentrations of total CoQ10, but this can be alleviated by simultaneous supplementation with CoQ10.

Effects of football fitness training on lymphedema and upper-extremity function in women after treatment for breast cancer: a randomized trial.

BACKGROUND: Breast cancer survivors are encouraged to be physically active. A recent review suggests that football training is an effective exercise modality for women across the lifespan, positively influencing health variables such as strength, fitness and social well-being. However, football is a contact sport, potentially posing an increased risk of trauma-related injury. Against this backdrop, breast cancer survivors are advised to avoid trauma or injury to the affected or at-risk arm in order to protect against lymphedema onset or exacerbation. The aim of this study was therefore to evaluate the feasibility and safety of Football Fitness training in relation to lymphedema and upper-extremity function after treatment for breast cancer. MATERIAL AND METHODS: Sixty-eight women aged 18-75 years, who had received surgery for stage I-III breast cancer and completed (neo) adjuvant chemotherapy and/or radiotherapy within five years, were randomized (2:1) to a Football Fitness group (FFG, n = 46) or a control group (CON, n = 22) for twelve months. Secondary analyses using linear mixed models were performed to assess changes in upper-body morbidity, specifically arm lymphedema (inter-arm volume % difference, dual energy X-ray absorptiometry; extracellular fluid (L-Dex), bioimpedance spectroscopy), self-reported breast and arm symptoms (EORTC breast cancer-specific questionnaire (BR23) and upper-extremity function (DASH questionnaire) at baseline, six- and twelve-month follow-up. RESULTS: We observed similar point prevalent cases of lymphedema between groups at all time points, irrespective of measurement method. At the six-month post-baseline assessment, reductions in L-Dex (extracellular fluid) were found in FFG versus CON. These significant findings were not maintained at the twelve-month assessment. No difference between groups was observed for inter-limb volume difference %, nor any of the remaining outcomes. CONCLUSION: While superiority of Football Fitness was not observed, the results support that participation in Football Fitness training is feasible and suggests no negative effects on breast cancer-specific upper-body morbidity, including lymphedema. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov. NCT03284567.

One year of Football Fitness improves L1-L4 BMD, postural balance, and muscle strength in women treated for breast cancer.

PURPOSE: To examine efficacy of 12 months Football Fitness offered twice per week on bone mineral density (BMD), bone turnover markers (BTM), postural balance, muscle strength, and body composition in women treated for early-stage breast cancer (BC). METHODS: Women treated for early-stage BC were randomized to Football Fitness (FFG, n = 46) or control (CON, n = 22) in a 2:1 ratio for 12 months, with assessments performed at baseline, 6 months and 12 months. Outcomes were total body-, lumbar spine- and proximal femur BMD, total body lean and fat mass, leg muscle strength, postural balance, and plasma amino-terminal propeptide of type 1 procollagen (P1NP), osteocalcin, and C-terminal telopeptide of type 1 collagen (CTX). Intention-to-treat (ITT) analyses and per-protocol analyses (≥50% attendance in FFG) were performed using linear mixed models. RESULTS: Participants in FFG completing the 12-month intervention (n = 33) attended 0.8 (SD = 0.4) sessions per week. Intention to treat analysis of mean changes over 12 months showed significant differences (p<.05) in L1-L4 BMD (0.029 g/cm2 , 95%CI: 0.001 to 0.057), leg press strength (7.2 kg, 95%CI: 0.1 to 14.3), and postural balance (-4.3 n need of support, 95%CI: -8.0 to -0.7) favoring FFG compared to CON. In the per-protocol analyses, L1-L4 and trochanter major BMD were improved (p = .012 and .030, respectively) in FFG compared with CON. No differences were observed between groups in BTMs in the ITT or per protocol analyses. CONCLUSION: One year of Football Fitness training may improve L1-L4 BMD, leg muscle strength, and postural balance in women treated for early-stage breast cancer.

High bone mineral density in lifelong trained female team handball players and young elite football players.

PURPOSE: Low bone mineral density (BMD) and fractures are a major concern in the female population and preventative strategies are needed. Whether team sports participation may reduce age-related bone loss in elderly women is still uncertain. METHODS: One hundred and thirty healthy, non-smoking women participated in this cross-sectional study, i.e., elderly (60-80 years) team handball players (EH, n = 35), elderly untrained controls (EC, n = 35), young (18-30 years) elite football players (YF, n = 30) and young untrained controls (YC, n = 30). A whole-body and two regional dual-energy X-ray absorptiometry (DXA) scans were performed to evaluate BMD and a blood sample was collected for measurement of bone turnover markers (BTMs). RESULTS: EH had higher BMD in all regions of the lumbar spine, except for L1, compared to EC (8-10%), and higher BMD in the femoral Ward's triangle (9%) and trochanter (7%) of the left leg. Furthermore, EH had higher mean leg BMD (8%) and whole-body BMD (5%) than EC. EH and YC had similar BMD in femoral trochanter, L1-L4 and mean leg despite an age difference of ~ 40 years. YF had higher BMD in all regions of the proximal femur (18-29%) and lumbar spine (12-16%) compared to YC, as well as higher mean leg BMD (20%) and whole-body BMD (13%). Sclerostin was 14% lower in EH compared to EC. YF showed higher PINP (98%), osteocalcin (57%), and CTX (83%) compared to YC. CONCLUSION: Lifelong team handball training and elite football training are associated with superior bone mineralization and changed bone turnover in elderly and young women.

Dietary habits, metabolic health and vitamin D status in Greenlandic children.

OBJECTIVE: To compare the dietary habits of children living in northern villages and in the capital of Greenland, given the reported transition from traditional to westernised diet in adults over recent decades, and to explore the association between consumption of marine mammals and fish (MMF) and the children's metabolic profile and vitamin D status. DESIGN: Children answered an FFQ encompassing sixty-four individual food types pooled into six food categories. Their pubertal stage, body fat, fitness level, metabolic profile (non-HDL-cholesterol, glycated Hb, insulin, glucose, high-sensitivity C-reactive protein) as well as serum 25-hydroxyvitamin D (25(OH)D) concentration were evaluated. SETTING: Siorapaluk and Qaanaaq (north of Greenland) and Nuuk (west). PARTICIPANTS: Children aged 6-18 years (n 177). RESULTS: MMF were most frequently eaten by children from Siorapaluk (mean (sd): 73·4 (14·1) times/month), followed by children from Qaanaaq (37·0 (25·0) times/month), and least often eaten by children from Nuuk (23·7 (24·6) times/month; P < 0·001). Children from Qaanaaq consumed 'junk food' more frequently (P < 0·001) and fruits and vegetables less frequently (P < 0·01) than children from Nuuk. MMF consumption was positively associated with serum 25(OH)D concentration (P < 0·05), but the overall prevalence of vitamin D deficiency was high (18 %). No association was found between MMF consumption and metabolic parameters. CONCLUSIONS: The dietary transition and influence of western diets have spread to the north of Greenland and only the most remote place consumed a traditional diet highly based on MMF. We found no strong associations of MMF consumption with metabolic health, but a positive association with vitamin D status.

Cardiovascular and metabolic health effects of team handball training in overweight women: Impact of prior experience.

PURPOSE: We tested the hypothesis that participation in small-sided team handball training could provide beneficial effects on cardiovascular and metabolic parameters in overweight premenopausal women with special focus on the importance of prior team handball experience. METHODS: A 16-week RCT training intervention was conducted in overweight premenopausal women randomized into three groups: a team handball training group without prior experience (UN; n = 13), a team handball group with prior experience (EXP; n = 10), and an inactive control group (CON; n = 9). Both UN and EXP completed 1.6 ± 0.3 training sessions per week with average heart rates of 84 ± 5 and 85 ± 9% of maximal heart rate, respectively. Cardiovascular and metabolic parameters were assessed before and after the intervention. RESULTS: Compared to CON, UN had significant increases in VO2max  (7 ± 4%) and intermittent endurance performance (26 ± 14%) as well as reduced total fat mass (4 ± 6%), total fat percentage (4 ± 5%), and android fat mass (7 ± 12%), respectively (all P < .05). Compared to UN and CON, EXP displayed increased left ventricular mass and left ventricular mass index (both P < .05) after the training period. There were no significant changes between any of the groups in muscle mass, blood lipids, resting heart rate, and blood pressure (all P > .05). CONCLUSION: Small-sided team handball training in overweight premenopausal women resulted in improvement of VO2max and body composition for participants with minimal team handball experience, indicating that prior team handball experience is not a prerequisite for improving physiological parameters of importance for health. Furthermore, EXP displayed cardiac adaptations, including increased left ventricular mass and left ventricular mass index.

Determination and validation of peak fat oxidation in endurance-trained men using an upper body graded exercise test.

Peak fat oxidation rate (PFO) and the intensity that elicits PFO (Fatmax ) are commonly determined by a validated graded exercise test (GE) on a cycling ergometer with indirect calorimetry. However, for upper body exercise fat oxidation rates are not well elucidated and no protocol has been validated. Thus, our aim was to test validity and inter-method reliability for determination of PFO and Fatmax in trained men using a GE protocol applying double poling on a ski-ergometer. PFO and Fatmax were assessed during two identical GE tests (GE1 and GE2) and validated against separated short continuous exercise bouts (SCE) at 35%, 50%, and 65% of V̇O2peak on the ski-ergometer in 10 endurance-trained men (V̇O2peak : 65.1 ± 1.0 mL·min-1 ·kg-1 , mean ± SEM). Between GE tests no differences were found in PFO (GE1: 0.42 ± 0.03; GE2: 0.45 ± 0.03 g·min-1 , P = .256) or Fatmax (GE1: 41 ± 2%; GE2: 43 ± 3% of V̇O2peak , P = .457) and the intra-individual coefficient of variation (CV) was 8 ± 2% and 11 ± 2% for PFO and Fatmax , respectively. Between GE and SCE tests, PFO (GEavg : 0.44 ± 0.03; SCE; 0.47 ± 0.06 g·min-1 , P = .510) was not different, whereas a difference in Fatmax (GEavg : 42 ± 2%; SCE: 52 ± 4% of V̇O2peak , P = .030) was observed with a CV of 17 ± 4% and 15 ± 4% for PFO and Fatmax , respectively. In conclusion, GE has a high day-to-day reliability in determination of PFO and Fatmax in trained men, whereas it is unclear if PFO and Fatmax determined by GE reflect continuous exercise in general.

Variation in mitochondrial respiratory capacity and myosin heavy chain composition in repeated muscle biopsies.

Skeletal muscle is a heterogeneous tissue and it is essential to know the methodological variation and reliability when measuring aspects of muscle function. We assessed the methodological and biological variation when measuring mitochondrial respiratory capacity (MRC), citrate synthase (CS) activity and myosin heavy chain (MHC) composition in muscle biopsies from nine healthy male participants, and in addition we assessed variation in MRC in isolated mitochondria and yeast suspension. We analysed MRC, CS activity and MHC composition in duplicates (intra-biopsy variation) to quantify the methodological variation, as well as the biological variation from multiple muscle biopsies (inter-biopsy variation) obtained at different sites of the same muscle. Three muscle biopsies (B1, B2 and B3) were obtained from each subject in m. vastus lateralis. Two of the biopsies were from the same leg and one from the other leg. For MRC, intra-biopsy coefficient of variation (CV) was 8.4% and inter-biopsy CV was 13.3%. For MHC type I, IIa and IIx intra-biopsy CV was 8.3, 6.0 and 22.3%, respectively. Inter-biopsy CV for these MHC types were 21.5, 15.4 and 42.0%, respectively. For CS activity intra-biopsy CV was 0.6% and inter-biopsy CV was 15.3%. No differences between B1, B2 and B3 were detected for MRC, CS activity or MHC composition.

Peak Fat Oxidation is not Independently Related to Ironman Performance in Women.

The aim of the present study was to investigate if peak fat oxidation rate (PFO) is related to Ironman performance in female athletes. Thirty-six female Ironman athletes (age: 34±1 yrs, [21-45 yrs.] SEM [Range]) with a BMI of 22.1±2.0 kg/m2 [18.8-28.4 kg/m2], a body fat percentage of 24.8±1.0% [9.0-37.0%] and a V̇O2peak of 53.0±1.3 ml/min/kg [36.5-70.5 ml/min/kg] were tested in the laboratory prior to the Ironman Copenhagen 2017. Race time ranged from 9:17:07 to 15:23:48 with mean race time being 11:57:26 h:min:s (717 min). By simple linear regression analyses we found associations between race time and P FO (r2=0.22, p<0.005), V̇O2peak (r2=0.65, p<0.0001) and the relative exercise intensity eliciting PFO (Fatmax) (r2=0.35, p=0.0001). Furthermore, associations were found between race time and body fat percentage (r2=0.44, p<0.0001) and age (r2=0.16, p<0.05). By means of multiple regression analysis, V̇O2peak was the only statistically significant variable explaining 64% of the variation in race time (adj. r2=0.64, p<0.005). In conclusion, these results demonstrate that PFO is not independently related to Ironman performance in a heterogeneous group of female athletes. Interestingly, V̇O2peak alone was able to predict 64% of the variation in Ironman race times.

A randomized double-blind study of testosterone replacement therapy or placebo in testicular cancer survivors with mild Leydig cell insufficiency (Einstein-intervention).

BACKGROUND: Elevated serum levels of luteinizing hormone and slightly decreased serum levels of testosterone (mild Leydig cell insufficiency) is a common hormonal disturbance in testicular cancer (TC) survivors. A number of studies have shown that low serum levels of testosterone is associated with low grade inflammation and increased risk of metabolic syndrome. However, so far, no studies have evaluated whether testosterone substitution improves metabolic dysfunction in TC survivors with mild Leydig cell insufficiency. METHODS/DESIGN: This is a single-center, randomized, double-blind, placebo-controlled study, designed to evaluate the effect of testosterone replacement therapy in TC survivors with mild Leydig cell insufficiency. Seventy subjects will be randomized to receive either testosterone replacement therapy or placebo. The subjects will be invited for an information meeting where informed consent will be obtained. Afterwards, a 52-weeks treatment period begins in which study participants will receive a daily dose of transdermal testosterone or placebo. Dose adjustment will be made three times during the initial 8 weeks of the study to a maximal daily dose of 40 mg of testosterone in the intervention arm. Evaluation of primary and secondary endpoints will be performed at baseline, 26 weeks post-randomization, at the end of treatment (52 weeks) and 3 months after completion of treatment (week 64). DISCUSSION: This study is the first to investigate the effect of testosterone substitution in testicular cancer survivors with mild Leydig cell insufficiency. If positive, it may change the clinical handling of testicular cancer survivors with borderline low levels of testosterone. TRIAL REGISTRATION: ClinicalTrials.gov : NCT02991209 (November 25, 2016).

Temporary impact of blood donation on physical performance and hematologic variables in women.

BACKGROUND: No former studies have examined how blood donation influences physical performance in women, who due to menstruation may have a slower recovery of performance. Therefore, the aim of this study was to clarify how VO2peak , time trial (TT) performance, and hematologic variables are affected in 18 iron-sufficient (plasma ferritin [P-ferritin] > 30 µg/L) women after a standard 450-mL blood donation. STUDY DESIGN AND METHODS: VO2peak , TT performance, and blood variables were measured at baseline and 3, 7, 14, 21, and 28 days after blood donation in 18 iron-sufficient women. Anthropometrics were measured at baseline and Day 28. RESULTS: VO2peak was reduced by 7.5 ± 1.1% from 2973 ± 87 mL/min at baseline to 2765 ± 73 mL/min 3 days after blood donation and remained below baseline until 28 days. The TT performance was reduced by 5.2 ± 1.0% from baseline (868 ± 31 sec) to Day 3 (915 ± 29 sec), but was not different from baseline 14 days after blood donation. Blood hemoglobin (B-Hb) concentration declined by 7.6 ± 2.1% from 8.4 ± 0.1 to 7.8 ± 0.1 mmol/L at baseline and on Day 3, respectively. P-ferritin at baseline was 58 ± 7 µg/L and it decreased (55 ± 3%) to a nadir of 24 ± 3 µg/L 28 days after blood donation and remained lower at 36 ± 4 µg/L after 90 days. CONCLUSION: VO2peak and B-Hb were only recovered 28 days after a blood donation whereas TT performance was back to baseline 14 days after blood donation.

Hepatic mitochondrial oxidative phosphorylation is normal in obese patients with and without type 2 diabetes.

KEY POINTS: Hepatic insulin resistance in patients with obesity or type 2 diabetes has been suggested to result from hepatic mitochondrial dysfunction. High-resolution respirometry (HRR) can be used to assess oxidative phosphorylation by measuring the mitochondrial oxygen consumption rate in the individual complexes of the mitochondria. By using HRR, the present study demonstrates no difference in hepatic mitochondrial oxidative phosphorylation among subjects with obesity with or without type 2 diabetes and non-obese controls. Furthermore, the amount of mitochondria, assessed by the citrate synthase activity, is not different between the three groups. Together the present findings indicate that hepatic mitochondrial oxidative phosphorylation capacity is not impaired in patients with obesity or type 2 diabetes. ABSTRACT: Obese patients with type 2 diabetes (T2DM) and without type 2 diabetes (OB) are characterized by high hepatic lipid content and hepatic insulin resistance. This may be linked to impaired hepatic mitochondrial oxidative phosphorylation (OXPHOS) capacity. The aim of the present study was to investigate and compare hepatic mitochondrial OXPHOS capacity in T2DM, OB and non-obese controls (CON). Seventeen obese patients (nine OB and eight T2DM) and six CON patients had perioperative liver biopsies taken. Samples were divided into three parts to measure (1) complex I, II and IV linked respiration, (2) citrate synthase (CS) activity and (3) lipid droplet (LD) size and area (% of total tissue area filled by LDs). State 3 respiration of complex I, II and IV and the CS activity did not differ in OB, T2DM and CON. LD size was significantly higher in T2DM compared with CON, and LD area tended (P = 0.10) to be higher in T2DM and OB compared with CON. The present findings indicate that hepatic OXPHOS capacity is not different in patients with markedly different weight and glycaemic control. Furthermore, the results do not support impaired hepatic mitochondrial respiratory capacity playing a major role in the development of obesity-induced type 2 diabetes.

Effects of immobilization and aerobic training on proteins related to intramuscular substrate storage and metabolism in young and older men.

PURPOSE: Aging and inactivity lead to skeletal muscle metabolic inflexibility, but the underlying molecular mechanisms are not entirely elucidated. Therefore, we investigated how muscle lipid and glycogen stores and major regulatory proteins were affected by short-term immobilization followed by aerobic training in young and older men. METHODS: 17 young (23 ± 1 years, 24 ± 1 kg m(-2), and 20 ± 2% body fat) and 15 older men (68 ± 1 years; 27 ± 1 kg m(-2), and 29 ± 2% body fat) underwent 2 weeks' one leg immobilization followed by 6 weeks' cycle training. Biopsies were obtained from m. vastus lateralis just before immobilization (at inclusion), after immobilization, and the after 6 weeks' training. The biopsies were analyzed for muscle substrates; muscle perilipin protein (PLIN), glycogen synthase (GS), synaptosomal-associated protein of 23 kDa (SNAP23) protein content, and muscle 3-hydroxyacyl-CoA dehydrogenase (HAD) activity RESULTS: The older men had higher intramuscular triglyceride (IMTG) (73 %) and Glycogen (16%) levels compared to the young men, and IMTG tended to increase with immobilization. PLIN2 and 3 protein content increased with immobilization in the older men only. The young men had higher GS (74%) protein compared to the older men. Immobilization decreased and training restored HAD activity, GS and SNAP23 protein content in young and older men. CONCLUSION: Evidence of age-related metabolic inflexibility is presented, seen as body fat and IMTG accumulation. The question arises as to whether IMTG accumulation in the older men is caused by or leading to the increase in PLIN2 and 3 protein content. Training decreased body fat and IMTG levels in both young and older men; hence, training should be prioritized to reduce the detrimental effect of aging on metabolism.

Effect of regional muscle location but not adiposity on mitochondrial biogenesis-regulating proteins.

PURPOSE: The aim of this study was to determine if the expression of the mitochondrial biogenesis-regulating proteins SIRT1, SIRT3 and PGC-1alpha in human skeletal muscle is influenced by adiposity. METHOD: Twenty-nine male subjects were recruited into three groups: control (n = 10), obese (n = 10) and post-obese (n = 9). Intentionally, groups were matched by age, aerobic capacity and in addition the control and post-obese groups also by BMI. Muscle biopsies were obtained from the m. deltoid and vastus lateralis. PGC-1alpha, SIRT1 and SIRT3 protein expression was analyzed by Western blot. RESULT: PGC-1alpha, SIRT1 and SIRT3 protein expression was similar regardless of the level of adiposity. Only a main effect of group on SIRT1 protein showed a trend toward higher expression in post-obese than control and obese (P = 0.09). Despite similar muscle fiber-type composition (previously reported), PGC-1alpha, SIRT1 and SIRT3 protein expression was higher in leg compared to arm muscle in all groups (P < 0.05). CONCLUSION: This study shows that PGC-1alpha, SIRT1 and SIRT3 protein expression in basal conditions was not altered in humans with different levels of adiposity but similar aerobic capacity. The expression of PGC-1alpha, SIRT1 and SIRT3 was higher in vastus lateralis than in deltoid muscle, indicating that local rather than systemic factors prevail in regulating the level of expression of these proteins.

Positive effects of 1-year football and strength training on mechanical muscle function and functional capacity in elderly men.

PURPOSE: A decline in physical capacity takes place with increasing age that negatively affects overall physical function including work ability and the ability to perform typical activities of daily living (ADL). The overall aim of the present study was to determine the neuromuscular adaptations to long-term (1 year) football and strength training in older untrained adults, and to assess the concurrent effect on functional ADL capacity. METHODS: Twenty-seven healthy elderly males (68.2 ± 3.2 years) were randomly assigned to 12 months of either recreational football training (FT: n = 10), strength training (ST: n = 9) or served as inactive controls (CON: n = 8). Recreational football training consisted of small-sided training sessions whereas strength training consisted of high intensity exercises targeting the lower extremity and upper body. Maximal thigh muscle strength and rate of force development (RFD) were assessed with isokinetic dynamometry, while postural balance and vertical jumping performance were evaluated using force plate analysis. Furthermore, functional ability was evaluated by stair-ascent and chair-rising testing. RESULTS: A total of nine, nine and seven participants from FT, ST and CON, respectively, were included in the analysis. Both exercise regimens led to substantial gains in functional ability, evidenced by 24 and 18 % reduced stair-ascent time, and 32 and 21 % increased chair-rising performance in FT and ST, respectively (all P < 0.05). Long-term strength training led to increased concentric (14 %; P < 0.01) and isometric (23 %; P < 0.001) quadriceps and isometric hamstring strength (44 %; P < 0.0001), whereas football training mainly resulted in enhanced hamstring strength (18 %, P < 0.05) and RFD (89 %, P < 0.0001). CONCLUSIONS: Long-term (1 year) strength training led to increased quadriceps and hamstring strength, whereas the adaptations to football training mainly included enhanced strength and rapid force capacity of the hamstring muscles. Gains in functional ability were observed in response to both training regimens, evidenced by reduced stair-ascent time and increased chair-rising performance. Long-term football exercise and strength training both appear to be effective interventional strategies to improve factors of importance for ADL by counteracting the age-related decline in lower limb strength and functional capacity among old male adults. This could potentially be a way to improve work ability of senior workers.

Skeletal muscle mitochondrial H2 O2 emission increases with immobilization and decreases after aerobic training in young and older men.

Currently, it is not known whether impaired mitochondrial function contributes to human ageing or whether potential impairments in mitochondrial function with age are secondary to physical inactivity. The present study investigated mitochondrial respiratory function and reactive oxygen species emission at a predefined membrane potential in young and older men subjected to 2 weeks of one-leg immobilization followed by 6 weeks of aerobic cycle training. Immobilization increased reactive oxygen species emission and decreased ATP generating respiration. Subsequent aerobic training reversed these effects. By contrast, age had no effect on the measured variables. The results of the present study support the notion that increased mitochondrial reactive oxygen species production mediates the detrimental effects seen after physical inactivity and that ageing per se does not cause mitochondrial dysfunction. Mitochondrial dysfunction, defined as increased oxidative stress and lower capacity for energy production, may be seen with ageing and may cause frailty, or it could be that it is secondary to physical inactivity. We studied the effect of 2 weeks of one-leg immobilization followed by 6 weeks of supervised cycle training on mitochondrial function in 17 young (mean ± SEM: 23 ± 1 years) and 15 older (68 ± 1 years) healthy men. Submaximal H2 O2 emission and respiration were measured simultaneously at a predefined membrane potential in isolated mitochondria from skeletal muscle using two protocols: pyruvate + malate (PM) and succinate + rotenone (SR). This allowed measurement of leak and ATP generating respiration from which the coupling efficiency can be calculated. The protein content of the anti-oxidants manganese superoxide dismuthase (MnSOD), CuZn superoxide dismuthase, catalase and gluthathione peroxidase 1 was measured by western blotting. Immobilization decreased ATP generating respiration using PM and increased H2 O2 emission using both PM and SR similarly in young and older men. Both were restored to baseline after the training period. Furthermore, MnSOD and catalase content increased with endurance training. The young men had a higher leak respiration at inclusion using PM and a higher membrane potential in State 3 using both substrate combinations. Collectively, the findings of the present study support the notion that increased mitochondrial reactive oxygen species mediates the detrimental effects seen after physical inactivity. Age, on the other hand, was not associated with impairments in anti-oxidant protein levels, mitochondrial respiration or H2 O2 emission using either protocol.

Preoperative ß-cell function in patients with type 2 diabetes is important for the outcome of Roux-en-Y gastric bypass surgery.

The majority of the patients with type 2 diabetes (T2DM) show remission after Roux-en-Y gastric bypass (RYGB). This is the result of increased postoperative insulin sensitivity and ß-cell secretion. The aim of the present study was to elucidate the importance of the preoperative ß-cell function in T2DM for the chance of remission after RYGB. Fifteen patients with and 18 without T2DM had 25 g oral (OGTT) and intravenous (IVGTT) glucose tolerance tests performed at inclusion, after a diet-induced weight loss, and 4 and 18 months after RYGB. Postoperative first phase insulin secretion rate (ISR) during the IVGTT and ß-cell glucose sensitivity during the OGTT increased in T2DM. Postoperative insulin sensitivity and the disposition index (DI) markedly increased in both groups. By stratifying the T2DM into two groups according to highest (T2DMhigh ) and lowest (T2DMlow ) baseline DI, a restoration of first phase ISR and ß-cell glucose sensitivity were seen only in T2DMhigh . Remission of type 2 diabetes was 71 and 38% in T2DMhigh and T2DMlow , respectively. Postoperative postprandial GLP-1 concentrations increased markedly, but did not differ between the groups. Our findings emphasize the importance of the preoperative of ß-cell function for remission of diabetes after RYGB.