Tiredness after work associates with less leisure-time physical activity.

Physical activities and sedentary behaviors take place in different contexts. This study aimed to determine if the context, total score, and leisure-time MET-index assessed by the Baecke questionnaire associate with each other or with sedentary behavior and physical activity outcomes from a 4-week accelerometer measurement in physically inactive adults with overweight. The item "After working I am tired" correlated negatively with items related to leisure-time physical activity and sports participation. The total Baecke Score showed weak but significant correlations with accelerometer-measured sedentary behavior, physical activity, daily steps, and mean activity intensity of the day (r = - 0.33, 0.41, 0.35, and 0.41, respectively). The associations strengthened when the Sport Index was omitted from the Score. The leisure-time MET-Index did not correlate with accelerometer-measured sedentary behavior or physical activity. Tiredness after working associated with less self-reported physical activity during leisure time. This suggests that better recovery from work-related stress could increase leisure-time physical activity, or increasing leisure-time physical activity could reduce tiredness after working. Moreover, among self-reportedly inactive adults with overweight, focusing the questionnaire on work and non-sport leisure time instead of total time might give more accurate estimates of sedentary behavior and physical activity when compared to accelerometry.The study is registered at ClinicalTrials.gov (NCT03101228, 05/04/2017).

Sedentary time associates detrimentally and physical activity beneficially with metabolic flexibility in adults with metabolic syndrome.

Metabolic flexibility (MetFlex) describes the ability to respond and adapt to changes in metabolic demand and substrate availability. The relationship between physical (in)activity and MetFlex is unclear. This study aimed to determine whether sedentary time, physical activity (PA), and cardiorespiratory fitness associate with MetFlex. Sedentary time, standing, and PA were measured with accelerometers for 4 weeks in 64 sedentary adults with metabolic syndrome [37 women, 27 men; 58.3 (SD 6.8) years]. Fitness (V̇o2max; mL·kg-1·min-1) was measured with graded maximal cycle ergometry. MetFlex was assessed with indirect calorimetry as the change in respiratory exchange ratio (ΔRER) from fasting to insulin stimulation with hyperinsulinemic-euglycemic clamp and from low-intensity to maximal exercise. Carbohydrate (CHOox) and fat oxidation (FATox) were calculated from respiratory gases. High sedentary time associated with higher fasting RER [ß = 0.35 (95% confidence interval: 0.04, 0.67)], impaired insulin-stimulated MetFlex (ΔRER) [ß=-0.41 (-0.72, -0.09)], and lower fasting FATox [ß=-0.36 (-0.67, -0.04)]. Standing associated with lower fasting RER [ß=-0.32 (-0.62, -0.02)]. Higher standing time and steps/day associated with higher fasting FATox [ß = 0.31 (0.01, 0.61), and ß = 0.26 (0.00, 0.53)]. Light-intensity and total PA associated with better insulin-stimulated MetFlex [ß = 0.33 (0.05, 0.61)], and ß = 0.33 (0.05, 0.60)]. Higher V̇o2max associated with higher CHOox during maximal exercise [ß = 0.81 (0.62, 1.00)], as well as during insulin stimulation [ß = 0.43 (0.13, 0.73)]. P values are less than 0.05 for all associations. Sedentary time and PA associate with MetFlex. Reducing sitting and increasing PA of even light intensity might aid in the prevention of metabolic diseases in risk populations through their potential effects on energy metabolism.NEW & NOTEWORTHY High accelerometer-assessed sedentary time associates with metabolic inflexibility measured during hyperinsulinemic-euglycemic clamp in adults with metabolic syndrome, and more light-intensity and total physical activity associate with more metabolic flexibility. Physical activity behaviors may thus play an important role in the regulation of fuel metabolism. This highlights the potential of reduced sedentary time and increased physical activity of any intensity to induce metabolic health benefits and help in disease prevention in risk populations.

Effects of reduced sedentary time on resting, exercise and post-exercise blood pressure in inactive adults with metabolic syndrome - a six-month exploratory RCT.

Evidence on the long-term effects of reducing sedentary behaviour (SB) on blood pressure (BP) is scarce. Therefore, we performed a sub-analysis of the BP effects of a six-month intervention that aimed at reducing SB by 1 h/day and replacing it with non-exercise activities. Sixty-four physically inactive and sedentary adults with metabolic syndrome (58% female, 58 [SD 7] years, BP 143/88 [16/9] mmHg, SB 10 [1] h/day) were randomised into intervention (INT, n = 33) and control (CON, n = 31) groups. Resting BP and BP at each stage during and after a graded maximal bicycle ergometer test were measured before and after the intervention. SB, standing, moderate-to-vigorous physical activity (MVPA), and light physical activity (LPA) were measured in six-second intervals at baseline and during the whole six-month intervention using hip-worn accelerometers. The analyses were adjusted for BP medication status. The intervention resulted in a 40 min/day reduction in SB and concomitant 20 min/day increase in MVPA. Resting systolic BP was lower in the CON group before and after the intervention. No group x time interactions were observed in resting BP or BP during exercise at submaximal or maximal intensities, or during recovery. The changes in LPA and MVPA were inversely correlated with the changes in BP during light-to-moderate intensity exercise. An intervention that resulted in a 40 min/day reduction in SB for six months was not sufficient at influencing BP at rest, during or after exercise in adults with metabolic syndrome. However, successfully increasing LPA or MVPA might lower BP during light-to-moderate-intensity activities.

The effects of a 6-month intervention aimed to reduce sedentary time on skeletal muscle insulin sensitivity: a randomized controlled trial.

Sedentary behavior (SB) and physical inactivity associate with impaired insulin sensitivity. We investigated whether an intervention aimed at a 1-h reduction in daily SB during 6 mo would improve insulin sensitivity in the weight-bearing thigh muscles. Forty-four sedentary inactive adults [mean age 58 (SD 7) yr; 43% men] with metabolic syndrome were randomized into intervention and control groups. The individualized behavioral intervention was supported by an interactive accelerometer and a mobile application. SB, measured with hip-worn accelerometers in 6-s intervals throughout the 6-mo intervention, decreased by 51 (95% CI 22-80) min/day and physical activity (PA) increased by 37 (95% CI 18-55) min/day in the intervention group with nonsignificant changes in these outcomes in the control group. Insulin sensitivity in the whole body and in the quadriceps femoris and hamstring muscles, measured with hyperinsulinemic-euglycemic clamp combined with [18F]fluoro-deoxy-glucose PET, did not significantly change during the intervention in either group. However, the changes in hamstring and whole body insulin sensitivity correlated inversely with the change in SB and positively with the changes in moderate-to-vigorous PA and daily steps. In conclusion, these results suggest that the more the participants were able to reduce their SB, the more their individual insulin sensitivity increased in the whole body and in the hamstring muscles but not in quadriceps femoris. However, according to our primary randomized controlled trial results, this kind of behavioral interventions targeted to reduce sedentariness may not be effective in increasing skeletal muscle and whole body insulin sensitivity in people with metabolic syndrome at the population level.NEW & NOTEWORTHY Aiming to reduce daily SB by 1 h/day had no impact on skeletal muscle insulin sensitivity in the weight-bearing thigh muscles. However, successfully reducing SB may increase insulin sensitivity in the postural hamstring muscles. This emphasizes the importance of both reducing SB and increasing moderate-to-vigorous physical activity to improve insulin sensitivity in functionally different muscles of the body and thus induce a more comprehensive change in insulin sensitivity in the whole body.

Effects of reducing sedentary behavior on cardiorespiratory fitness in adults with metabolic syndrome: A 6-month RCT.

INTRODUCTION: Poor cardiorespiratory fitness (CRF) is associated with adverse health outcomes. Previous observational and cross-sectional studies have suggested that reducing sedentary behavior (SB) might improve CRF. Therefore, we investigated the effects of a 6-month intervention of reducing SB on CRF in 64 sedentary inactive adults with metabolic syndrome in a non-blind randomized controlled trial. MATERIALS AND METHODS: In the intervention group (INT, n = 33), the aim was to reduce SB by 1 h/day for 6 months without increasing exercise training. Control group (CON, n = 31) was instructed to maintain their habitual SB and physical activity. Maximal oxygen uptake (VO2max ) was measured by maximal graded bicycle ergometer test with respiratory gas measurements. Physical activity and SB were measured during the whole intervention using accelerometers. RESULTS: Reduction in SB did not improve VO2max statistically significantly (group × time p > 0.05). Maximal absolute power output (Wmax ) did not improve significantly but increased in INT compared to CON when scaled to fat free mass (FFM) (at 6 months INT 1.54 [95% CI: 1.41, 1.67] vs. CON 1.45 [1.32, 1.59] Wmax /kgFFM , p = 0.036). Finally, the changes in daily step count correlated positively with the changes in VO2max scaled to body mass and FFM (r = 0.31 and 0.30, respectively, p < 0.05). DISCUSSION: Reducing SB without adding exercise training does not seem to improve VO2max in adults with metabolic syndrome. However, succeeding in increasing daily step count may increase VO2max .

Reducing Sedentary Time and Whole-Body Insulin Sensitivity in Metabolic Syndrome: A 6-Month Randomized Controlled Trial.

PURPOSE: This study aimed to investigate whether a reduction in daily sedentary behavior (SB) improves insulin sensitivity in adults with metabolic syndrome in 6 months, without adding intentional exercise training. METHODS: Sixty-four sedentary inactive middle-age adults with overweight and metabolic syndrome (mean (SD) age, 58 (7) yr; mean (SD) body mass index, 31.6 (4.3) kg·m -2 ; 27 men) were randomized into intervention and control groups. The 6-month individualized behavioral intervention supported by an interactive accelerometer and a mobile application aimed at reducing daily SB by 1 h compared with baseline. Insulin sensitivity by hyperinsulinemic euglycemic clamp, body composition by air displacement plethysmography, and fasting blood samples were analyzed before and after the intervention. SB and physical activity were measured with hip-worn accelerometers throughout the intervention. RESULTS: SB decreased by 40 (95% confidence interval, 17-65) min·d -1 , and moderate-to-vigorous physical activity increased by 20 (95% confidence interval, 11-28) min·d -1 on average in the intervention group with no significant changes in these outcomes in the control group. After 6 months, fasting plasma insulin decreased (~1 mU·L -1 ) in the intervention group compared with the control group (time-group, P = 0.0081), but insulin sensitivity did not change in either group. The changes in body mass or adiposity did not differ between groups. Among all participants, the changes in SB and body mass correlated inversely with the change in insulin sensitivity ( r = -0.31, -0.44; P = 0.025, 0.0005, respectively). CONCLUSIONS: An intervention aimed at reducing daily SB resulted in slightly decreased fasting insulin, but had no effects on insulin sensitivity or body adiposity. However, as the change in insulin sensitivity associated with the changes in SB and body mass, multifaceted interventions targeting to weight loss are likely to be beneficial in improving whole-body insulin sensitivity.

Cool-Water Immersion Reduces Postexercise Quadriceps Femoris Muscle Perfusion More Than Cold-Water Immersion.

PURPOSE: The muscle perfusion response to postexercise cold-water immersion (CWI) is not well understood. We examined the effects of graded postexercise CWI upon global and regional quadriceps femoris muscle perfusion using positron emission tomography and [15O]H2O. METHODS: Using a matched-group design, 30 healthy men performed cycle ergometer exercise at 70% V̇O2peak to a core body temperature of 38°C, followed by either 10 min of CWI at 8°C, 22°C, or seated rest (control). Quadriceps muscle perfusion; thigh and calf cutaneous vascular conductance; intestinal, muscle, and local skin temperatures; thermal comfort; mean arterial pressure; and heart rate were assessed at preexercise, postexercise, and after CWI. RESULTS: Global quadriceps perfusion was reduced beyond the predefined minimal clinically relevant threshold (0.75 mL per 100 g·min-1) in 22°C water versus control (difference (95% confidence interval (CI)), -2.5 (-3.9 to -1.1) mL per 100 g·min-1). Clinically relevant decreases in muscle perfusion were observed in the rectus femoris (-2.0 (-3.0 to -1.0) mL per 100 g·min-1) and vastus lateralis (-3.5 (-4.9 to -2.0) mL per 100 g·min-1) in 8°C water, and in the vastus lateralis (-3.3 (-4.8 to -1.9) mL per 100 g·min-1) in 22°C water versus control. The mean effects for vastus intermedius and vastus medialis perfusion were not clinically relevant. Clinically relevant decreases in thigh and calf cutaneous vascular conductance were observed in both cooling conditions. CONCLUSIONS: The present findings revealed that less noxious CWI (22°C) promoted clinically relevant postexercise decreases in global quadriceps muscle perfusion, whereas noxious cooling (8°C) elicited no effect.

Influence of the Duration and Timing of Data Collection on Accelerometer-Measured Physical Activity, Sedentary Time and Associated Insulin Resistance.

Accelerometry is a commonly used method to determine physical activity in clinical studies, but the duration and timing of measurement have seldom been addressed. We aimed to evaluate possible changes in the measured outcomes and associations with insulin resistance during four weeks of accelerometry data collection. This study included 143 participants (median age of 59 (IQR9) years; mean BMI of 30.7 (SD4) kg/m2; 41 men). Sedentary and standing time, breaks in sedentary time, and different intensities of physical activity were measured with hip-worn accelerometers. Differences in the accelerometer-based results between weeks 1, 2, 3 and 4 were analyzed by mixed models, differences during winter and summer by two-way ANOVA, and the associations between insulin resistance and cumulative means of accelerometer results during weeks 1 to 4 by linear models. Mean accelerometry duration was 24 (SD3) days. Sedentary time decreased after three weeks of measurement. More physical activity was measured during summer compared to winter. The associations between insulin resistance and sedentary behavior and light physical activity were non-significant after the first week of measurement, but the associations turned significant in two to three weeks. If the purpose of data collection is to reveal associations between accelerometer-measured outcomes and tenuous health outcomes, such as insulin sensitivity, data collection for at least three weeks may be needed.

Exercise intensity regulates cytokine and klotho responses in men.

BACKGROUND: Short-term exercise training programs that consist of moderate intensity endurance training or high intensity interval training have become popular choices for healthy lifestyle modifications, with as little as two weeks of training being shown to improve cardiorespiratory fitness and whole-body glucose metabolism. An emerging concept in exercise biology is that exercise stimulates the release of cytokines and other factors into the blood that contribute to the beneficial effects of exercise on metabolism, but whether these factors behave similarly in response to moderate and high intensity short term training is not known. Here, we determined the effects of two short-term exercise training programs on the concentrations of select secreted cytokines and Klotho, a protein involved in anti-aging. METHODS: Healthy, sedentary men (n = 22) were randomized to moderate intensity training (MIT) or sprint intensity training (SIT) treatment groups. SIT consisted of 6 sessions over 2 weeks of 6 × 30 s all out cycle ergometer sprints with 4 min of recovery between sprints. MIT consisted of 6 sessions over 2 weeks of cycle ergometer exercise at 60% VO2peak, gradually increasing in duration from 40 to 60 min. Blood was taken before the intervention and 48 h after the last training session, and glucose uptake was measured using [18F]FDG-PET/CT scanning. Cytokines were measured by multiplex and Klotho concentrations by ELISA. RESULTS: Both training protocols similarly increased VO2peak and decreased fat percentage and visceral fat (P < 0.05). MIT and SIT training programs both reduced the concentrations of IL-6, Hepatocyte Growth Factor (HGF) and Leptin. Interestingly, MIT, but not SIT increased monocyte chemoattractant protein-1 (MCP-1) concentrations, an exercise-induced cytokine, as well as Klotho concentrations. CONCLUSION: Short-term exercise training at markedly different intensities similarly improves cardiovascular fitness but results in intensity-specific changes in cytokine responses to exercise.

Effects of Different Exercise Training Protocols on Gene Expression of Rac1 and PAK1 in Healthy Rat Fast- and Slow-Type Muscles.

PURPOSE: Rac1 and its downstream target PAK1 are novel regulators of insulin and exercise-induced glucose uptake in skeletal muscle. However, it is not yet understood how different training intensities affect the expression of these proteins. Therefore, we studied the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on Rac1 and PAK1 expression in fast-type (gastrocnemius, GC) and slow-type (soleus, SOL) muscles in rats after HIIT and MICT swimming exercises. METHODS: The mRNA expression was determined using qPCR and protein expression levels with reverse-phase protein microarray (RPPA). RESULTS: HIIT significantly decreased Rac1 mRNA expression in GC compared to MICT (p = 0.003) and to the control group (CON) (p = 0.001). At the protein level Rac1 was increased in GC in both training groups, but only the difference between HIIT and CON was significant (p = 0.02). HIIT caused significant decrease of PAK1 mRNA expression in GC compared to MICT (p = 0.007) and to CON (p = 0.001). At the protein level, HIIT increased PAK1 expression in GC compared to MICT and CON (by ∼17%), but the difference was not statistically significant (p = 0.3, p = 0.2, respectively). There were no significant differences in the Rac1 or PAK1 expression in SOL between the groups. CONCLUSION: Our results indicate that HIIT, but not MICT, decreases Rac1 and PAK1 mRNA expression and increases the protein expression of especially Rac1 but only in fast-type muscle. These exercise training findings may reveal new therapeutic targets to treat patients with metabolic diseases.

Both sedentary time and physical activity are associated with cardiometabolic health in overweight adults in a 1 month accelerometer measurement.

The aim of this study was to examine the associations of cardiometabolic health markers with device-measured sedentary behavior (SB) duration and different intensities of physical activity (PA) among overweight working-aged adults with low self-reported PA levels. This cross-sectional analysis included 144 subjects (42 men) with mean age of 57 (SD 6.5) years and mean BMI of 31.7 (SD 4) kg/m2. SB and standing time, breaks in sedentary time, light PA (LPA) and moderate-to-vigorous PA (MVPA) were measured for 4 consecutive weeks (mean 25 days, SD 4) with hip-worn accelerometers. Fasting plasma glucose, insulin, HbA1c, triglycerides and total cholesterol, HDL and LDL were measured from venous blood samples. HOMA-IR index was calculated as a surrogate of insulin resistance. The associations were examined using linear models. LPA, MVPA, and daily steps associated with better insulin sensitivity and favorable plasma lipid profile, when adjusted for age, sex and BMI, whereas greater proportion of SB associated with insulin resistance and unfavorable lipid profile. As all PA intensities associated with better cardiometabolic health, the total daily duration of PA may be more relevant than intensity in maintaining metabolic health in overweight adults, if the current guidelines for PA are not met.Trial Registration: ClinicalTrials.gov NCT03101228, registered 05/04/2017, https://clinicaltrials.gov/show/NCT03101228 .

Change in abdominal, but not femoral subcutaneous fat CT-radiodensity is associated with improved metabolic profile after bariatric surgery.

BACKGROUND AND AIMS: Computed tomography (CT)-derived adipose tissue radiodensity represents a potential noninvasive surrogate marker for lipid deposition and obesity-related metabolic disease risk. We studied the effects of bariatric surgery on CT-derived adipose radiodensities in abdominal and femoral areas and their relationships to circulating metabolites in morbidly obese patients. METHODS AND RESULTS: We examined 23 morbidly obese women who underwent CT imaging before and 6 months after bariatric surgery. Fifteen healthy non-obese women served as controls. Radiodensities of the abdominal subcutaneous (SAT) and visceral adipose tissue (VAT), and the femoral SAT, adipose tissue masses were measured in all participants. Circulating metabolites were measured by NMR. At baseline, radiodensities of abdominal fat depots were lower in the obese patients as compared to the controls. Surprisingly, radiodensity of femoral SAT was higher in the obese as compared to the controls. In the abdominal SAT depot, radiodensity strongly correlated with SAT mass (r = -0.72, p < 0.001). After surgery, the radiodensities of abdominal fat increased significantly (both p < 0.01), while femoral SAT radiodensity remained unchanged. Circulating ApoB/ApoA-I, leucine, valine, and GlycA decreased, while glycine levels significantly increased as compared to pre-surgical values (all p < 0.05). The increase in abdominal fat radiodensity correlated negatively with the decreased levels of ApoB/ApoA-I ratio, leucine and GlycA (all p < 0.05). The increase in abdominal SAT density was significantly correlated with the decrease in the fat depot mass (r = -0.66, p = 0.002). CONCLUSION: Higher lipid content in abdominal fat depots, and lower content in femoral subcutaneous fat, constitute prominent pathophysiological features in morbid obesity. Further studies are needed to clarify the role of non-abdominal subcutaneous fat in the pathogenesis of obesity. CLINICAL TRIAL REGISTRATION NUMBER: NCT01373892.

Exercise training improves adipose tissue metabolism and vasculature regardless of baseline glucose tolerance and sex.

INTRODUCTION: We investigated the effects of a supervised progressive sprint interval training (SIT) and moderate-intensity continuous training (MICT) on adipocyte morphology and adipose tissue metabolism and function; we also tested whether the responses were similar regardless of baseline glucose tolerance and sex. RESEARCH DESIGN AND METHODS: 26 insulin-resistant (IR) and 28 healthy participants were randomized into 2-week-long SIT (4-6×30 s at maximum effort) and MICT (40-60 min at 60% of maximal aerobic capacity (VO2peak)). Insulin-stimulated glucose uptake and fasting-free fatty acid uptake in visceral adipose tissue (VAT), abdominal and femoral subcutaneous adipose tissues (SATs) were quantified with positron emission tomography. Abdominal SAT biopsies were collected to determine adipocyte morphology, gene expression markers of lipolysis, glucose and lipid metabolism and inflammation. RESULTS: Training increased glucose uptake in VAT (p<0.001) and femoral SAT (p<0.001) and decreased fatty acid uptake in VAT (p=0.01) irrespective of baseline glucose tolerance and sex. In IR participants, training increased adipose tissue vasculature and decreased CD36 and ANGPTL4 gene expression in abdominal SAT. SIT was superior in increasing VO2peak and VAT glucose uptake in the IR group, whereas MICT reduced VAT fatty acid uptake more than SIT. CONCLUSIONS: Short-term training improves adipose tissue metabolism both in healthy and IR participants independently of the sex. Adipose tissue angiogenesis and gene expression was only significantly affected in IR participants.

Bone Marrow Metabolism Is Impaired in Insulin Resistance and Improves After Exercise Training.

CONTEXT: Exercise training improves bone mineral density, but little is known about the effects of training on bone marrow (BM) metabolism. BM insulin sensitivity has been suggested to play an important role in bone health and whole-body insulin sensitivity. OBJECTIVE: To study the effects of exercise training on BM metabolism. DESIGN: Randomized controlled trial. SETTING: Clinical research center. PARTICIPANTS: Sedentary healthy (n = 28, 40-55 years, all males) and insulin resistant (IR) subjects (n = 26, 43-55 years, males/females 16/10). INTERVENTION: Two weeks of sprint interval training or moderate-intensity continuous training. MAIN OUTCOME MEASURES: We measured femoral, lumbar, and thoracic BM insulin-stimulated glucose uptake (GU) and fasting free fatty acid uptake (FFAU) using positron-emission tomography and bone turnover markers from plasma. RESULTS: At baseline, GU was highest in lumbar, followed by thoracic, and lowest in femoral BM (all Ps < 0.0001). FFAU was higher in lumbar and thoracic than femoral BM (both Ps < 0.0001). BM FFAU and femoral BM GU were higher in healthy compared to IR men and in females compared to males (all Ps < 0.05). Training increased femoral BM GU similarly in all groups and decreased lumbar BM FFAU in males (all Ps < 0.05). Osteocalcin and PINP were lower in IR than healthy men and correlated positively with femoral BM GU and glycemic status (all Ps < 0.05). CONCLUSIONS: BM metabolism differs regarding anatomical location. Short-term training improves BM GU and FFAU in healthy and IR subjects. Bone turnover rate is decreased in insulin resistance and associates positively with BM metabolism and glycemic control. CLINICAL TRIAL REGISTRATION NUMBER: NCT01344928.

Changes in quadriceps femoris muscle perfusion following different degrees of cold-water immersion.

We examined the influence of graded cold-water immersion (CWI) on global and regional quadriceps muscle perfusion with positron emission tomography (PET) and [15O]H2O. In 30 healthy men [33 ± 8 yr; 81 ± 10 kg; 184 ± 5 cm; percentage body fat: 13 ± 5%; peak oxygen uptake (V̇o2peak): 47 ± 8 mL·kg-1·min-1] quadriceps perfusion, thigh and calf cutaneous vascular conductance (CVC), intestinal, muscle, and local skin temperatures, thermal comfort, mean arterial pressure, and heart rate were assessed before and after 10 min of CWI at 8°C, 15°C, or 22°C. Global quadriceps perfusion did not change beyond a clinically relevant threshold (0.75 mL·100 g·min-1) in any condition and was similar between conditions {range of differences [95% confidence interval (CI)]: 0.1 mL·100 g·min-1 (-0.9 to 1.2 mL·100 g·min-1) to 0.9 mL·100 g·min-1 (-0.2 to 1.9 mL·100 g·min-1)}. Muscle perfusion was greater in vastus intermedius (VI) compared with vastus lateralis (VL) (2.2 mL·100 g·min-1; 95% CI 1.5 to 3.0 mL·100 g·min-1) and rectus femoris (RF) (2.2 mL·100 g·min-1; 1.4 to 2.9 mL·100 g·min-1). A clinically relevant increase in VI muscle perfusion after immersion at 8°C and a decrease in RF muscle perfusion at 15°C were observed. A clinically relevant increase in perfusion was observed in VI in 8°C compared with 22°C water (2.3 mL·100 g·min-1; 1.1 to 3.5 mL·100 g·min-1). There were no clinically relevant between-condition differences in thigh CVC. Our findings suggest that CWI (8-22°C) does not reduce global quadriceps muscle perfusion to a clinically relevant extent; however, colder water increases (8°C) deep muscle perfusion and reduces (15°C) superficial muscle (RF) perfusion in the quadriceps muscle.NEW & NOTEWORTHY Using positron emission tomography, we report for the first time muscle perfusion heterogeneity in the quadriceps femoris in response to different degrees of cold-water immersion (CWI). Noxious CWI temperatures (8°C) increase perfusion in the deep quadriceps muscle, whereas superficial quadriceps muscle perfusion is reduced in cooler (15°C) water. Therefore, these data have important implications for the selection of CWI approaches used in the treatment of soft tissue injury, while also increasing our understanding of the potential mechanisms underpinning CWI.

Predicting Skeletal Muscle and Whole-Body Insulin Sensitivity Using NMR-Metabolomic Profiling.

PURPOSE: Abnormal lipoprotein and amino acid profiles are associated with insulin resistance and may help to identify this condition. The aim of this study was to create models estimating skeletal muscle and whole-body insulin sensitivity using fasting metabolite profiles and common clinical and laboratory measures. MATERIAL AND METHODS: The cross-sectional study population included 259 subjects with normal or impaired fasting glucose or type 2 diabetes in whom skeletal muscle and whole-body insulin sensitivity (M-value) were measured during euglycemic hyperinsulinemic clamp. Muscle glucose uptake (GU) was measured directly using [18F]FDG-PET. Serum metabolites were measured using nuclear magnetic resonance (NMR) spectroscopy. We used linear regression to build the models for the muscle GU (Muscle-insulin sensitivity index [ISI]) and M-value (whole-body [WB]-ISI). The models were created and tested using randomly selected training (n = 173) and test groups (n = 86). The models were compared to common fasting indices of insulin sensitivity, homeostatic model assessment-insulin resistance (HOMA-IR) and the revised quantitative insulin sensitivity check index (QUICKI). RESULTS: WB-ISI had higher correlation with actual M-value than HOMA-IR or revised QUICKI (ρ = 0.83 vs -0.67 and 0.66; P < 0.05 for both comparisons), whereas the correlation of Muscle-ISI with the actual skeletal muscle GU was not significantly stronger than HOMA-IR's or revised QUICKI's (ρ = 0.67 vs -0.58 and 0.59; both nonsignificant) in the test dataset. CONCLUSION: Muscle-ISI and WB-ISI based on NMR-metabolomics and common laboratory measurements from fasting serum samples and basic anthropometrics are promising rapid and inexpensive tools for determining insulin sensitivity in at-risk individuals.

Exercise Training Modulates Gut Microbiota Profile and Improves Endotoxemia.

INTRODUCTION: Intestinal metabolism and microbiota profiles are impaired in obesity and insulin resistance. Moreover, dysbiotic gut microbiota has been suggested to promote systemic low-grade inflammation and insulin resistance through the release of endotoxins particularly lipopolysaccharides. We have previously shown that exercise training improves intestinal metabolism in healthy men. To understand whether changes in intestinal metabolism interact with gut microbiota and its release of inflammatory markers, we studied the effects of sprint interval (SIT) and moderate-intensity continuous training (MICT) on intestinal metabolism and microbiota in subjects with insulin resistance. METHODS: Twenty-six, sedentary subjects (prediabetic, n = 9; type 2 diabetes, n = 17; age, 49 [SD, 4] yr; body mass index, 30.5 [SD, 3]) were randomized into SIT or MICT. Intestinal insulin-stimulated glucose uptake (GU) and fatty acid uptake (FAU) from circulation were measured using positron emission tomography. Gut microbiota composition was analyzed by 16S rRNA gene sequencing and serum inflammatory markers with multiplex assays and enzyme-linked immunoassay kit. RESULTS: V˙O2peak improved only after SIT (P = 0.01). Both training modes reduced systematic and intestinal inflammatory markers (tumor necrosis factor-α, lipopolysaccharide binding protein) (time P < 0.05). Training modified microbiota profile by increasing Bacteroidetes phylum (time P = 0.03) and decreasing Firmicutes/Bacteroidetes ratio (time P = 0.04). Moreover, there was a decrease in Clostridium genus (time P = 0.04) and Blautia (time P = 0.051). Only MICT decreased jejunal FAU (P = 0.02). Training had no significant effect on intestinal GU. Colonic GU associated positively with Bacteroidetes and inversely with Firmicutes phylum, ratio Firmicutes/Bacteroidetes and Blautia genus. CONCLUSIONS: Intestinal substrate uptake associates with gut microbiota composition and whole-body insulin sensitivity. Exercise training improves gut microbiota profiles and reduces endotoxemia.

Myocardial Blood Flow and Metabolic Rate of Oxygen Measurement in the Right and Left Ventricles at Rest and During Exercise Using 15O-Labeled Compounds and PET.

Aims: Simultaneous measurement of right (RV) and left ventricle (LV) myocardial blood flow (MBF), oxygen extraction fraction (OEF), and oxygen consumption (MVO2) non-invasively in humans would provide new possibilities to understand cardiac physiology and different patho-physiological states. Methods: We developed and tested an optimized novel method to measure MBF, OEF, and MVO2 simultaneously both in the RV and LV free wall (FW) using positron emission tomography in healthy young men at rest and during supine bicycle exercise. Results: Resting MBF was not significantly different between the three myocardial regions. Exercise increased MBF in the LVFW and septum, but MBF was lower in the RV compared to septum and LVFW during exercise. Resting OEF was similar between the three different myocardial regions (~70%) and increased in response to exercise similarly in all regions. MVO2 increased approximately two to three times from rest to exercise in all myocardial regions, but was significantly lower in the RV during exercise as compared to septum LVFW. Conclusion: MBF, OEF, and MVO2 can be assessed simultaneously in the RV and LV myocardia at rest and during exercise. Although there are no major differences in the MBF and OEF between LV and RV myocardial regions in the resting myocardium, MVO2 per gram of myocardium appears to be lower the RV in the exercising healthy human heart due to lower mean blood flow. The presented method may provide valuable insights for the assessment of MBF, OEF and MVO2 in hearts in different pathophysiological states.

Effects of short-term sprint interval and moderate-intensity continuous training on liver fat content, lipoprotein profile, and substrate uptake: a randomized trial.

Type 2 diabetes (T2D) and increased liver fat content (LFC) alter lipoprotein profile and composition and impair liver substrate uptake. Exercise training mitigates T2D and reduces LFC, but the benefits of different training intensities in terms of lipoprotein classes and liver substrate uptake are unclear. The aim of this study was to evaluate the effects of moderate-intensity continuous training (MICT) or sprint interval training (SIT) on LFC, liver substrate uptake, and lipoprotein profile in subjects with normoglycemia or prediabetes/T2D. We randomized 54 subjects (normoglycemic group, n = 28; group with prediabetes/T2D, n = 26; age = 40-55 yr) to perform either MICT or SIT for 2 wk and measured LFC with magnetic resonance spectroscopy, lipoprotein composition with NMR, and liver glucose uptake (GU) and fatty acid uptake (FAU) using PET. At baseline, the group with prediabetes/T2D had higher LFC, impaired lipoprotein profile, and lower whole body insulin sensitivity and aerobic capacity compared with the normoglycemic group. Both training modes improved aerobic capacity (P < 0.001) and lipoprotein profile (reduced LDL and increased large HDL subclasses; all P < 0.05) with no training regimen (SIT vs. MICT) or group effect (normoglycemia vs. prediabetes/T2D). LFC tended to be reduced in the group with prediabetes/T2D compared with the normoglycemic group posttraining (P = 0.051). When subjects were divided according to LFC (high LFC, >5.6%; low LFC, <5.6%), training reduced LFC in subjects with high LFC (P = 0.009), and only MICT increased insulin-stimulated liver GU (P = 0.03). Short-term SIT and MICT are effective in reducing LFC in subjects with fatty liver and in improving lipoprotein profile regardless of baseline glucose tolerance. Short-term MICT is more efficient in improving liver insulin sensitivity compared with SIT. NEW & NOTEWORTHY In the short term, both sprint interval training and moderate-intensity continuous training (MICT) reduce liver fat content and improve lipoprotein profile; however, MICT seems to be preferable in improving liver insulin sensitivity.

TGF-ß2 is an exercise-induced adipokine that regulates glucose and fatty acid metabolism.

Exercise improves health and well-being across diverse organ systems, and elucidating mechanisms underlying the beneficial effects of exercise can lead to new therapies. Here, we show that transforming growth factor-ß2 (TGF-ß2) is secreted from adipose tissue in response to exercise and improves glucose tolerance in mice. We identify TGF-ß2 as an exercise-induced adipokine in a gene expression analysis of human subcutaneous adipose tissue biopsies after exercise training. In mice, exercise training increases TGF-ß2 in scWAT, serum, and its secretion from fat explants. Transplanting scWAT from exercise-trained wild type mice, but not from adipose tissue-specific Tgfb2-/- mice, into sedentary mice improves glucose tolerance. TGF-ß2 treatment reverses the detrimental metabolic effects of high fat feeding in mice. Lactate, a metabolite released from muscle during exercise, stimulates TGF-ß2 expression in human adipocytes. Administration of the lactate-lowering agent dichloroacetate during exercise training in mice decreases circulating TGF-ß2 levels and reduces exercise-stimulated improvements in glucose tolerance. Thus, exercise training improves systemic metabolism through inter-organ communication with fat via a lactate-TGF-ß2-signaling cycle.