FDG uptake and walking ability

Includes bibliographical references.Motor impairments of the upper and lower extremities are common symptoms of multiple sclerosis (MS). While some peripheral effects like muscle weakness and loss of balance have been shown to influence these symptoms, central nervous system activity has not been fully elucidated. The purpose of this study was to determine if alterations in glucose uptake were associated with motor impairments in patients with multiple sclerosis. Eight patients with multiple sclerosis (4 men) and 8 sex matched healthy controls performed 15 minutes of treadmill walking at a self-selected pace, during which ≈ 322 MBq of the positron emission tomography glucose analogue [18F]-Fluorodeoxyglucose was injected. Immediately after the cessation of walking, participants underwent positron emission tomography imaging. Patients with MS had lower FDG uptake in ≈ 40% of the brain compared to the healthy controls (pFWE-corr > 0.001, qFDR-corr -0.75, P < 0.032). Within patients with MS only 3 of the 15 regions showed significant correlations: insula (r = -0.74, P = 0.036), hippocampus (r = -0.72, P = 0.045), and calcarine sulcus (r = -0.77, P = 0.026). This data suggests that walking impairments in patients with MS may be due to network wide alterations in glucose metabolism. Understanding how brain activity and metabolism are altered in patients with MS may allow for better measures of disability and disease status within this clinical population.Published with support from the Colorado State University Libraries Open Access Research and Scholarship Fund

The effect of nitric oxide synthase inhibition with and without inhibition of prostaglandins on blood flow in different human skeletal muscles

Purpose Animal studies suggest that the inhibition of nitric oxide synthase (NOS) affects blood flow differently in different skeletal muscles according to their muscle fibre type composition (oxidative vs glycolytic). Quadriceps femoris (QF) muscle consists of four different muscle parts: vastus intermedius (VI), rectus femoris (RF), vastus medialis (VM), and vastus lateralis (VL) of which VI is located deep within the muscle group and is generally regarded to consist mostly of oxidative muscle fibres.Methods We studied the effect of NOS inhibition on blood flow in these four different muscles by positron emission tomography in eight young healthy men at rest and during one-leg dynamic exercise, with and without combined blockade with prostaglandins.Results At rest blood flow in the VI (2.6 +/- 1.1 ml/100 g/min) was significantly higher than in VL (1.9 +/- 0.6 ml/100 g/min, p = 0.015) and RF (1.7 +/- 0.6 ml/100 g/min, p = 0.0015), but comparable to VM (2.4 +/- 1.1 ml/100 g/min). NOS inhibition alone or with prostaglandins reduced blood flow by almost 50% (p < 0.001), but decrements were similar in all four muscles (drug x muscle interaction, p = 0.43). During exercise blood flow was also the highest in VI (45.4 +/- 5.5 ml/100 g/min) and higher compared to VL (35.0 +/- 5.5 ml/100 g/min), RF (38.4 +/- 7.4 ml/100 g/min), and VM (36.2 +/- 6.8 ml/100 g/min). NOS inhibition alone did not reduce exercise hyperemia (p = 0.51), but combined NOS and prostaglandin inhibition reduced blood flow during exercise (p = 0.002), similarly in all muscles (drug x muscle interaction, p = 0.99).Conclusion NOS inhibition, with or without prostaglandins inhibition, affects blood flow similarly in different human QF muscles both at rest and during low-to-moderate intensity exercise

Aerobic exercise modulates anticipatory reward processing via the mu-opioid receptor system

Physical exercise modulates food reward and helps control body weight. The endogenous mu-opioid receptor (MOR) system is involved in rewarding aspects of both food and physical exercise, yet interaction between endogenous opioid release following exercise and anticipatory food reward remains unresolved. Here we tested whether exercise-induced opioid release correlates with increased anticipatory reward processing in humans. We scanned 24 healthy lean men after rest and after a 1 h session of aerobic exercise with positron emission tomography (PET) using MOR-selective radioligand [C-11]carfentanil. After both PET scans, the subjects underwent a functional magnetic resonance imaging (fMRI) experiment where they viewed pictures of palatable versus nonpalatable foods to trigger anticipatory food reward responses. Exercise-induced changes in MOR binding in key regions of reward circuit (amygdala, thalamus, ventral and dorsal striatum, and orbitofrontal and cingulate cortices) were used to predict the changes in anticipatory reward responses in fMRI. Exercise-induced changes in MOR binding correlated negatively with the exercise-induced changes in neural anticipatory food reward responses in orbitofrontal and cingulate cortices, insula, ventral striatum, amygdala, and thalamus: higher exercise-induced opioid release predicted higher brain responses to palatable versus nonpalatable foods. We conclude that MOR activation following exercise may contribute to the considerable interindividual variation in food craving and consumption after exercise, which might promote compensatory eating and compromise weight control

Exercise training improves biventricular oxidative metabolism and left ventricular efficiency in patients with dilated cardiomyopathy

AbstractObjectivesThe aim of this study was to determine the effect of exercise training on myocardial oxidative metabolism and efficiency in patients with idiopathic dilated cardiomyopathy (DCM) and mild heart failure (HF).BackgroundExercise training is known to improve exercise tolerance and quality of life in patients with chronic HF. However, little is known about how exercise training may influence myocardial energetics.MethodsTwenty clinically stable patients with DCM (New York Heart Association classes I through III) were prospectively separated into a training group (five-month training program; n = 9) and a non-trained control group (n = 11). Oxidative metabolism in both the right and left ventricles (RV and LV) was measured using [11C]acetate and positron emission tomography. Myocardial work power was measured using echocardiography. Myocardial efficiency for forward work was calculated as myocardial work power per mass/LV oxidative metabolism.ResultsSignificant improvements were noted in exercise capacity (Vo2) and ejection fraction in the training group, whereas no changes were observed in the non-trained group. Exercise training reduced both RV and LV oxidative metabolism and elicited a significant increase in LV forward work efficiency, although no significant changes were observed in the non-trained group.ConclusionsExercise training improves exercise tolerance and LV function. This is accompanied by a decrease in biventricular oxidative metabolism and enhanced forward work efficiency. Therefore, exercise training elicits an energetically favorable improvement in myocardial function and exercise tolerance in patients with DCM

Insulin-stimulated glucose uptake in skeletal muscle, adipose tissue and liver: A positron emission tomography study

Objective: Insulin resistance is reflected by the rates of reduced glucose uptake (GU) into the key insulin-sensitive tissues, skeletal muscle, liver and adipose tissue. It is unclear whether insulin resistance occurs simultaneously in all these tissues or whether insulin resistance is tissue specific. Design and methods: We measured GU in skeletal muscle, adipose tissue and liver and endogenous glucose production (EGP), in a single session using 18F-fluorodeoxyglucose with positron emission tomography (PET) and euglycemic–hyperinsulinemic clamp. The study population consisted of 326 subjects without diabetes from the CMgene study cohort. Results: Skeletal muscle GU less than 33 µmol/kg tissue/min and subcutaneous adipose tissue GU less than 11.5 µmol/kg tissue/min characterized insulin-resistant individuals. Men had considerably worse insulin suppression of EGP compared to women. By using principal component analysis (PCA), BMI inversely and skeletal muscle, adipose tissue and liver GU positively loaded on same principal component explaining one-third of the variation in these measures. The results were largely similar when liver GU was replaced by EGP in PCA. Liver GU and EGP were positively associated with aging. Conclusions: We have provided threshold values, which can be used to identify tissue-specific insulin resistance. In addition, we found that insulin resistance measured by GU was only partially similar across all insulin-sensitive tissues studied, skeletal muscle, adipose tissue and liver and was affected by obesity, aging and gender.</p

Myocardial Blood Flow and Metabolic Rate of Oxygen Measurement in the Right and Left Ventricles at Rest and During Exercise Using O-15-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 (similar to 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.</div

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 (4-6x30 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 (pPeer reviewe

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 x 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 Conclusion Short-term exercise training at markedly different intensities similarly improves cardiovascular fitness but results in intensity-specific changes in cytokine responses to exercise.</div

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/m(2); 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 Training Modulates Gut Microbiota Profile and Improves Endotoxemia

INRTRODUCTION: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 insulin resistance.METHODS:Twenty-six, sedentary subjects (prediabetic n=9, T2D n=17; age 49[SD 4] years; BMI 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 PET. Gut microbiota composition was analysed by 16S rRNA gene sequencing and serum inflammatory markers with multiplex assays and enzyme-linked immunoassay kit.RESULTS:VO2peak improved only after SIT (p=0.01). Both training modes reduced systematic and intestinal inflammatory markers (TNF α, LBP) (time pCONCLUSION:Intestinal substrate uptake associates with gut microbiota composition and activity and whole-body insulin sensitivity. Exercise training improves gut microbiota profiles and reduces endotoxemia.</p