Martina Zügel

Association between circulating irisin and insulin resistance in non-diabetic adults: A meta-analysis

INTRODUCTION Exogenous administration of recombinant irisin improves glucose metabolism. However, the association of endogenous circulating (plasma/serum) irisin with insulin resistance remains poorly delineated. This study was aimed to examine this association by meta-analyzing the current evidence without study design restriction in non-diabetic adults. MATERIALS/METHODS Peer-reviewed studies written in English from 3 databases were searched to December 2015. Studies that reported the association between circulating irisin and insulin resistance (or its reverse, insulin sensitivity) in non-diabetic non-pregnant adults (mean ages ≥18years) were included. The pooled correlation coefficient (r) and 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup analyses and meta-regression were performed to explore potential sources of heterogeneity. RESULTS Of the 195 identified publications, 17 studies from 15 articles enrolling 1912 participants reported the association between circulating irisin and insulin resistance. The pooled effect size was 0.15 (95% CI: 0.07 to 0.22) with a substantial heterogeneity (I(2)=55.5%). This association seemed to be modified by glycemic status (fasting blood glucose ≥6.1mmol/L versus <6.1mmol/L) and racial-ethnic difference (Asians versus Europeans versus Americans), but not by sex difference, sampling time-point, blood sample type, ELISA kits used, baseline age, or body mass index. Circulating irisin was inversely associated with insulin sensitivity (6 studies; r=-0.17, 95% CI: -0.25 to -0.09). CONCLUSIONS Circulating irisin is directly and positively associated with insulin resistance in non-diabetic adults. However, this association is rather small and requires further clarification, in particular by well-designed large epidemiological studies with overall, race-, and sex-specific analyses.

Basal and exercise induced label-free quantitative protein profiling of m. vastus lateralis in trained and untrained individuals.

UNLABELLED Morphological and metabolic adaptations of the human skeletal muscle to exercise are crucial to improve performance and prevent chronic diseases and metabolic disorders. In this study we investigated human skeletal muscle protein composition in endurance trained (ET) versus untrained individuals (UT) and its modulation by an acute bout of endurance exercise. Participants were recruited based on their VO2max and subjected to a bicycle exercise test. M. vastus lateralis biopsies were taken before and three hours after exercise. Muscle lysates were analyzed using off-gel LC-MS/MS. Relative protein abundances were compared between ET and UT at rest and after exercise. Comparing UT and ET, we identified 92 significantly changed proteins under resting conditions. Specifically, fiber-type-specific and proteins of the oxidative phosphorylation and tricarboxylic acid cycle were increased in ET. In response to acute exercise, 71 proteins in ET and 44 in UT were altered. Here, a decrease of proteins involved in energy metabolism accompanied with alterations of heat shock and proteasomal proteins could be observed. In summary, long-term endurance training increased the basal level of structural and mitochondrial proteins in skeletal muscle. In contrast, acute exercise resulted in a depletion of proteins related to substrate utilization, especially in trained athletes. BIOLOGICAL SIGNIFICANCE The investigation of the human skeletal muscle proteome in response to exercise may provide novel insights into the process of muscular plasticity. It is of importance in the development of exercise-based strategies in the prevention and therapy of many chronic inflammatory and degenerative diseases which are often accompanied by muscular deconditioning. Up to date, proteomic investigations of the human muscle proteome in adaptation to exercise are mainly focused on untrained individuals and often restricted to animal studies. In the present study we compare the protein composition in endurance trained athletes and untrained individuals in the resting muscle and its modulation in response to acute exercise. To our knowledge, we present the first comprehensive analysis of skeletal muscle proteome alterations in response to acute and long-term exercise intervention.

Effects of Acute Endurance Exercise on Plasma Protein Profiles of Endurance-Trained and Untrained Individuals over Time

Acute physical exercise and repeated exercise stimuli affect whole-body metabolic and immunologic homeostasis. The aim of this study was to determine plasma protein profiles of trained (EET, n = 19) and untrained (SED, n = 17) individuals at rest and in response to an acute bout of endurance exercise. Participants completed a bicycle exercise test at an intensity corresponding to 80% of their VO2max. Plasma samples were taken before, directly after, and three hours after exercise and analyzed using multiplex immunoassays. Seventy-eight plasma variables were included in the final analysis. Twenty-nine variables displayed significant acute exercise effects in both groups. Seven proteins differed between groups, without being affected by acute exercise. Among these A2Macro and IL-5 were higher in EET individuals while leptin showed elevated levels in SED individuals. Fifteen variables revealed group and time differences with elevated levels for IL-3, IL-7, IL-10, and TNFR2 in EET individuals. An interaction effect could be observed for nine variables including IL-6, MMP-2, MMP-3, and muscle damage markers. The proteins that differ between groups indicate a long-term exercise effect on plasma protein concentrations. These findings might be of importance in the development of exercise-based strategies in the prevention and therapy of chronic metabolic and inflammatory diseases and for training monitoring.

Pedometer intervention and weight loss in overweight and obese adults with Type 2 diabetes: a meta‐analysis

Although pedometer intervention is effective in increasing physical activity among adults with Type 2 diabetes, its impact on weight loss remains unclear. This meta‐analysis was aimed to assess whether pedometer intervention promotes weight loss.

Step Counter Use and Sedentary Time in Adults: A Meta-Analysis.

AbstractAlthough step counters are increasingly being used in walking programmes to promote sedentary behavior changes in adults, their effectiveness remains unknown. The aim of this meta-analysis of randomized controlled trials (RCTs) was to assess the effectiveness of step counter use in reducing sedentary time among adults.English-language RCTs from 3 databases were searched up to December 2014. Studies were included if they evaluated the effects of step counter use in adult populations and reported outcomes in sedentary time. Summary estimates (Cohen d with 95% confidence intervals [CIs]) were pooled using a random-effects model. Subgroup analyses and random-effects meta-regression analyses based on the characteristics of participants or interventions were conducted to explore their associations with sedentary time changes.Fifteen RCTs with a total sample size of 3262 adults were included. Step counter use was associated with a small but significant overall effect in reducing sedentary time (d = −0.20, 95% CI −0.33 to −0.07), equating to a reduction in sedentary time of ∼23 min/d compared with controls. Subgroup analyses showed that step counter use with a step goal was associated with significantly reduced sedentary time (d =− 0.32, 95% CI −0.53 to −0.11), whereas without, it had only a trend. A greater reduction in sedentary time was observed among step counter users employing objective methods than those employing subjective methods for measurement (P = 0.03). Effects of covariates on sedentary time changes were generally unclear.Step counter use is associated with reduced sedentary time among adults. Future studies are required to specify the step goal use and to employ objective as well as subjective methods for measuring both total and domain-specific sedentary time.

Carbohydrate Intake in Form of Gel Is Associated with Increased Gastrointestinal Distress but Not with Performance Differences Compared with Liquid Carbohydrate Ingestion during Simulated Long-Distance Triathlon

The ingestion of exogenous carbohydrates (CHO) during prolonged endurance exercise, such as long-distance triathlon, is considered beneficial with regard to performance. However, little is known about whether this performance benefit differs among different forms of CHO administration. To this end, the purpose of our study was to determine the impact of CHO ingestion from a semisolid source (GEL) on measures of performance and gastrointestinal (GI) comfort compared with CHO ingestion from a liquid source (LIQ). Nine well-trained triathletes participated in this randomized crossover study. Each participant completed a 60-min swim, 180-min bike exercise, and a 60-min all-out run in a laboratory environment under 2 conditions, once while receiving 67.2 ± 7.2 g · h-1 (M ± SD) of CHO from GEL and once while receiving 67.8 ± 4.2 g · h-1 of CHO from LIQ. The amount of fluid provided was matched among conditions. Respiratory exchange ratio (RER), blood glucose, and lactate as well as GI discomfort were assessed at regular intervals during the experiment. The distance covered during the final all-out run was not significantly different among participants ingesting GEL (11.81 ± 1.38 km) and LIQ (11.91 ± 1.53 km; p = .89). RER, blood glucose, and lactate did not differ significantly at any time during the experiment. Seven participants reported GI discomfort with GEL, and no athlete reported GI discomfort with LIQ (p = .016). This study suggests that administration of GEL does not alter long-distance triathlon performance when compared with LIQ, but GEL seems to be associated with reduced GI tolerance. Athletes should consider this a potential disadvantage of GEL administration during long-distance triathlon.

Ribosomal transcription is regulated by PGC-1alpha and disturbed in Huntington’s disease

PGC-1α is a versatile inducer of mitochondrial biogenesis and responsive to the changing energy demands of the cell. As mitochondrial ATP production requires proteins that derive from translation products of cytosolic ribosomes, we asked whether PGC-1α directly takes part in ribosomal biogenesis. Here, we show that a fraction of cellular PGC-1α localizes to the nucleolus, the site of ribosomal transcription by RNA polymerase I. Upon activation PGC-1α associates with the ribosomal DNA and boosts recruitment of RNA polymerase I and UBF to the rDNA promoter. This induces RNA polymerase I transcription under different stress conditions in cell culture and mouse models as well as in healthy humans and is impaired already in early stages of human Huntington’s disease. This novel molecular link between ribosomal and mitochondrial biogenesis helps to explain sarcopenia and cachexia in diseases of neurodegenerative origin.

Circulating irisin in patients with polycystic ovary syndrome: a meta-analysis

There is growing interest in exploring circulating (plasma/serum) irisin in polycystic ovary syndrome (PCOS) patients. This meta-analysis aimed to summarize the evidence assessing circulating irisin changes in this population. A systematic search was conducted in three databases: PubMed, Cochrane Library and Web of Science, for studies reporting irisin in PCOS patients compared with healthy controls or stratified by body mass index (BMI), or assessing irisin response to hyperinsulinemia. Effect sizes (Cohens d with 95% confidence intervals [CI]) were calculated using random-effects models. Eight studies with 918 PCOS patients and 528 healthy controls were included. Results showed that circulating irisin was higher in PCOS patients than in overall healthy controls (d = 0.37, 95% CI 0.05 to 0.70), but not compared with BMI-matched or age- and BMI-matched controls. Circulating irisin was higher in PCOS patients with higher BMI than lower (d = 0.36, 95% CI 0.16 to 0.56). Circulating irisin decreased 2 h later in response to euglycemic hyperinsulinemia in PCOS patients with a larger magnitude than healthy controls (d = -0.32, 95% CI -0.53 to -0.11). In summary, with adjustment for BMI, circulating irisin in PCOS patients seems comparable to healthy controls, but its response to hyperinsulinemia might be impaired.

High-resolution respirometry of fine-needle muscle biopsies in pre-manifest Huntington's disease expansion mutation carriers shows normal mitochondrial respiratory function

Alterations in mitochondrial respiration are an important hallmark of Huntington’s disease (HD), one of the most common monogenetic causes of neurodegeneration. The ubiquitous expression of the disease causing mutant huntingtin gene raises the prospect that mitochondrial respiratory deficits can be detected in skeletal muscle. While this tissue is readily accessible in humans, transgenic animal models offer the opportunity to cross-validate findings and allow for comparisons across organs, including the brain. The integrated respiratory chain function of the human vastus lateralis muscle was measured by high-resolution respirometry (HRR) in freshly taken fine-needle biopsies from seven pre-manifest HD expansion mutation carriers and nine controls. The respiratory parameters were unaffected. For comparison skeletal muscle isolated from HD knock-in mice (HdhQ111) as well as a broader spectrum of tissues including cortex, liver and heart muscle were examined by HRR. Significant changes of mitochondrial respiration in the HdhQ knock-in mouse model were restricted to the liver and the cortex. Mitochondrial mass as quantified by mitochondrial DNA copy number and citrate synthase activity was stable in murine HD-model tissue compared to control. mRNA levels of key enzymes were determined to characterize mitochondrial metabolic pathways in HdhQ mice. We demonstrated the feasibility to perform high-resolution respirometry measurements from small human HD muscle biopsies. Furthermore, we conclude that alterations in respiratory parameters of pre-manifest human muscle biopsies are rather limited and mirrored by a similar absence of marked alterations in HdhQ skeletal muscle. In contrast, the HdhQ111 murine cortex and liver did show respiratory alterations highlighting the tissue specific nature of mutant huntingtin effects on respiration.

Aerobic Interval Training and Cardiometabolic Health in Patients with Type 2 Diabetes: A Meta-Analysis

Vigorous to maximal aerobic interval training (INT) has received remarkable interest in improving cardiometabolic outcomes for type 2 diabetes patients recently, yet with inconsistent findings. This meta-analysis was aimed to quantify its effectiveness in type 2 diabetes. Randomized controlled trials (RCTs) were identified by searches of 3 databases to October 2017, which evaluated the effects of INT with a minimal training duration of 8 weeks vs. moderate-intensity continuous training (MICT) or non-exercise training (NET) among type 2 diabetes patients on outcomes including cardiorespiratory fitness, glycemic control, body composition, blood pressure, and lipid profiles. Weighted mean differences with 95% confidence intervals (CIs) were calculated with the random-effects model. Nine datasets from 7 RCTs with 189 patients were included. Compared with MICT, INT improved maximal oxygen consumption (VO2max) by 2.60 ml/kg/min (95% CI: 1.32 to 3.88 ml/kg/min, P <0.001) and decreased hemoglobin A1c (HbA1c) by 0.26% (95% CI: −0.46% to −0.07%, P = 0.008). These outcomes for INT were also significant vs. energy expenditure-matched MICT, with VO2max increased by 2.18 ml/kg/min (P = 0.04) and HbA1c decreased by 0.28% (P = 0.01). Yet their magnitudes of changes were larger compared with NET, with VO2max increased by 6.38 ml/kg/min (P <0.001) and HbA1c reduced by 0.83% (P = 0.004). Systolic blood pressure could be lowered by INT compared with energy expenditure-matched MICT or NET (both P <0.05), but other cardiometabolic markers and body composition were not significantly altered in general. In conclusion, despite a limited number of studies, INT improves cardiometabolic health especially for VO2max and HbA1c among patients with type 2 diabetes, and might be considered an alternative to MICT. Yet the optimal training protocols still require to be established.