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Measuring individual circadian phase is important to diagnose and treat circadian rhythm sleep-wake disorders and circadian misalignment, inform chronotherapy, and advance circadian science. Initial findings using blood transcriptomics to predict the circadian phase marker dim-light melatonin onset (DLMO) show promise. Alternatively, there are limited attempts using metabolomics to predict DLMO and no known omics-based biomarkers predict dim-light melatonin offset (DLMOff). We analyzed the human plasma metabolome during adequate and insufficient sleep to predict DLMO and DLMOff using one blood sample. Sixteen (8 male/8 female) healthy participants aged 22.4 ± 4.8 years (mean ± SD) completed an in-laboratory study with 3 baseline days (9 h sleep opportunity/night), followed by a randomized cross-over protocol with 9-h adequate sleep and 5-h insufficient sleep conditions, each lasting 5 days. Blood was collected hourly during the final 24 h of each condition to independently determine DLMO and DLMOff. Blood samples collected every 4 h were analyzed by untargeted metabolomics and were randomly split into training (68%) and test (32%) sets for biomarker analyses. DLMO and DLMOff biomarker models were developed using partial least squares regression in the training set followed by performance assessments using the test set. At baseline, the DLMOff model showed the highest performance (0.91 R2 and 1.1 ± 1.1 h median absolute error ± interquartile range [MdAE ± IQR]), with significantly ( p < 0.01) lower prediction error versus the DLMO model. When all conditions (baseline, 9 h, and 5 h) were included in performance analyses, the DLMO (0.60 R2; 2.2 ± 2.8 h MdAE; 44% of the samples with an error under 2 h) and DLMOff (0.62 R2; 1.8 ± 2.6 h MdAE; 51% of the samples with an error under 2 h) models were not statistically different. These findings show promise for metabolomics-based biomarkers of circadian phase and highlight the need to test biomarkers that predict multiple circadian phase markers under different physiological conditions.

PURPOSE This study aimed to determine if energy intake and appetite regulation differ in response to an acute bout of resistance exercise (REx) versus aerobic exercise (AEx). METHODS Physically inactive adults (n = 24, 35% ± 2% body fat, 50% female) completed three conditions: AEx (walking at 65%-70% heart rate max for 45 min), REx (1 set to failure of 12 exercises), and sedentary control (SED). Each condition was initiated in the postprandial state (35 min after breakfast). Appetite (visual analog scale for hunger, satiety, and prospective food consumption) and hormones (ghrelin, peptide YY (PYY), and glucagon-like peptide-1 (GLP-1)) were measured before and 30, 90, 120, 150, and 180 min after a standardized breakfast. Area under the curve was calculated using the trapezoid method. Ad libitum energy intake was evaluated at a lunch meal after the 180-min measurements. RESULTS No differences in ad libitum energy intake (REx, 991 ± 68; AEx, 937 ± 65; SED, 944 ± 76 kcal; P = 0.50) or appetite ratings (all, P > 0.05) were detected. The area under the curve for ghrelin, PYY, and GLP-1 were all lower after REx versus AEx (ghrelin: 130,737 ± 4928 for REx; 143,708 ± 7500 for AEx (P = 0.006); PYY: 20,540 ± 1177 for REx, 23,812 ± 1592 for AEx (P = 0.001); and GLP-1: 1314 ± 93 for REx, 1615 ± 110 for AEx (P = 0.013)). Neither exercise condition significantly differed from SED. CONCLUSIONS Acute REx lowers both orexigenic (ghrelin) and anorectic (PYY and GLP-1) gut peptides compared with acute AEx. Ad libitum energy intake did not increase compared with SED in either exercise condition, indicating both exercise modalities have appetite and energy intake suppressing effects. Future work is needed to determine if exercise of differing modalities influences chronic appetite regulation.

Objective The purpose of this study was to determine whether suppression of ovarian function (gonadotropin-releasing hormone agonist [GnRHAG ]) for 24 weeks in premenopausal women approaching menopause causes changes in body composition and a decline in free-living physical activity energy expenditure (PAEE) and whether endurance exercise training attenuates the changes. Methods Premenopausal women who were approaching menopause (mean [SD]: age 46 [3] years, BMI 26.3 [4.8] kg/m2 ) were randomized to 24 weeks of GnRHAG (n = 14), GnRHAG + Exercise (n = 11), or placebo (n = 9). Endurance exercise was performed 4 days per week with the goal of expending 200 to 300 kcal per session. Primary outcome measurements included body composition by dual-energy x-ray absorptiometry, total daily energy expenditure (TDEE), and PAEE by doubly labeled water, and resting energy expenditure (REE) by indirect calorimetry. Results Changes in TDEE, PAEE, REE, or body composition were not different between groups. However, within the GnRHAG group, fat mass increased (mean [SE]: total 1.7 [0.4] kg, trunk 0.9 [0.2] kg, leg 0.6 [0.2] kg) and fat-free leg mass decreased (mean [SE]: -0.4 [0.2] kg) significantly. Conclusions In premenopausal women approaching menopause, ovarian hormone suppression resulted in increased adiposity without alterations in TDEE, PAEE, or REE.

Introduction Exercise can cause a decrease in serum ionized calcium (iCa) concentration, which stimulates parathyroid hormone (PTH) secretion and activates bone resorption. We postulated that dermal Ca loss during cycling exercise is the major determinant of the serum iCa, PTH, and bone resorption (C-terminal telopeptide of type 1 collagen [CTX]) responses. Methods To investigate this, women (n = 13) and men (n = 12) age 18 to 45 yr performed the same exercise bout under cool (18°C) and warm (26°C) conditions. Exercise was 60 min of cycling at ~75% of peak aerobic power. Sweat samples were obtained during exercise using a skin patch method, and blood samples were obtained before and during exercise and during 60 min of recovery. Results Sweat volume and estimated sweat Ca loss were 50% higher for the warm condition than the cool condition. Despite this, there were no differences between thermal conditions in the changes (mean, 95% confidence interval [95% CI]) in iCa (cool, -0.07 mg·dL; 95% CI, -0.16 to 0.03); warm, -0.07 mg·dL; 95% CI, -0.20 to 0.05), PTH (cool, 34.4 pg·mL; 95% CI, 23.6-45.2; warm: 35.8 pg·mL; 95% CI, 22.4-49.1), or CTX (cool, 0.11 ng·mL; 95% CI, 0.08-0.13; warm, 0.15 ng·mL; 95% CI, 0.11-0.18). Adjusting for exercise-related shifts in plasma volume revealed a marked decline in vascular iCa content in the first 15 min of exercise (cool, -0.85 mg·dL; 95% CI, -1.01 to -0.68; warm, -0.85 mg·dL; 95% CI, -1.05 to -0.66), before substantial sweat Ca loss had occurred. Conclusions This indicates that dermal Ca loss was not the primary trigger for the increases in PTH and CTX during exercise. Further research is necessary to understand the causes and consequences of the disruption in Ca homeostasis during exercise and specifically the extravascular shift in iCa.

Many adults cite exercise as a primary strategy for losing weight, yet exercise alone is modestly effective for weight loss and results in variable weight loss responses. It is possible that some of the variability in weight loss may be explained by the time of day that exercise is performed. Few studies have directly compared the effects of exercise performed at different times of the day (i. e., morning versus evening exercise). Results from these existing studies are mixed with some studies demonstrating superior weight and fat mass loss from morning exercise, while other studies have found that evening exercise may be better for weight management. Exercise timing may alter modifiable lifestyle behaviors involved in weight management, such as non-exercise physical activity, energy intake, and sleep. The purpose of this review is to summarize evidence for and against time-of-day dependent effects of exercise on weight management. Although limited, we also review studies that have examined the effect of exercise timing on other lifestyle behaviors linked to body weight regulation. While exercise at any time of day is beneficial for health, understanding whether there is an optimal time of day to exercise may advance personalized treatment paradigms for weight management.

Objective The objectives of this study were to describe sitting, standing, and stepping patterns for people with lower limb amputation (LLA) and to compare sitting, standing, and stepping between people with dysvascular LLA and people with traumatic LLA. Methods Participants with dysvascular or traumatic LLA were included if their most recent LLA was at least 1 year earlier, they were ambulating independently with a prosthesis, and they were between 45 and 88 years old. Sitting, standing, and stepping were measured using accelerometry. Daily sitting, standing, and stepping times were expressed as percentages of waking time. Time spent in bouts of specified durations of sitting (90 minutes), standing (0–1, 1–5, and >5 minutes), and stepping (0–1, 1–5, and >5 minutes) was also calculated. Results Participants (N = 32; mean age = 62.6 [SD = 7.8] years; 84% men; 53% with dysvascular LLA) spent most of the day sitting (median = 77% [quartile 1 {Q1}–quartile 3 {Q3} = 67%–84%]), followed by standing (median = 16% [Q1–Q3 = 12%–27%]) and stepping (median = 6% [Q1–Q3 = 4%–9%]). One-quarter (median = 25% [Q1–Q3 = 16%–38%]) of sitting was accumulated in bouts of >90 minutes, and most standing and stepping was accrued in bouts of Conclusion Participants had high daily volumes of long durations of sitting. Further, these individuals accumulated most physical activity in bouts of Impact High levels of sedentary behavior and physical inactivity patterns may place people with LLA at greater mortality risk relative to the general population. Interventions to minimize sedentary behaviors and increase physical activity are potential strategies for improving poor outcomes of physical therapy after LLA.

BACKGROUND/OBJECTIVES: Individuals successful at weight loss maintenance engage in high amounts of physical activity (PA). Understanding how and when weight loss maintainers accumulate PA within a day and across the week may inform PA promotion strategies and recommendations for weight management. METHODS: We compared patterns of PA in a cohort of weight loss maintainers (WLM, n=28, maintaining ≥13.6 kg weight loss for ≥1 year, BMI 23.6 ± 2.3 kg/m(2)), controls without obesity (NC, n=30, BMI similar to current BMI of WLM, BMI 22.8 ± 1.9 kg/m(2)), and controls with overweight/obesity (OC, n=26, BMI similar to pre-weight loss BMI of WLM, 33.6 ± 5.1 kg/m(2)). PA was assessed during 7 consecutive days using the activPAL(™) activity monitor. The following variables were quantified; sleep duration, sedentary time (SED), light-intensity PA (LPA), moderate-to-vigorous intensity PA (MVPA), and steps. Data were examined to determine differences in patterns of PA across the week and across the day using mixed effect models. RESULTS: Across the week, WLM engaged in ≥60 minutes of MVPA on 73% of days, significantly more than OC (36%, p

BACKGROUND: Baseline cardiovascular fitness may be a significant predictor of future success in a comprehensive behavioral weight loss program (BWLP). Yet, few studies have examined the association between baseline fitness and future weight loss. PURPOSE: To determine the association between baseline fitness and changes in body weight and device-measured levels of moderate-to-vigorous physical activity (MVPA) during a BWLP. METHODS: Adults (n=85) were enrolled in an 18-month BWLP combining a calorie-restricted diet, group-based behavioral support, and 6 months of supervised exercise (progressing to 300 min/wk of moderate-intensity) followed by 12 months of unsupervised exercise. Data from 60 completers (age 41.0±9.5 years, BMI 34.6±4.2 kg/m2, 80% female) were used in this analysis. MVPA was measured over 1 week with the Sensewear Armband at months 0, 6, 12, and 18. Fitness (VO2max) was measured on a treadmill using indirect calorimetry and categorized based on published age and sex norms (Physical Fitness Specialist Certification Manual, 1997). A linear mixed effects model with unstructured covariance was used to examine the association between baseline fitness category and changes in body weight, total MVPA, and MVPA in bouts ≥10 min at the four time points. RESULTS: Of the 60 completers, 33% (n=20) were classified as having very poor fitness, 45% (n=27) poor, 18% (n=11) fair, 3% (n=2) good, and 0% (n=0) excellent or superior. Due to the low proportion of participants categorized as having fair or better fitness, we created a binary fitness variable (very poor vs. poor or better). Baseline BMI was higher in those in the very poor category compared to those in the poor or better category (36.2±4.2 vs 33.7±4.0, p=0.03). There were no significant differences between the two fitness categories in weight change at 6 or 12 months. However, at 18 months, mean weight loss was 4.3±1.7 kg in those in the very poor category and 8.2±1.2 kg in those in the poor or better category, with a marginally significant between-group difference (p=0.07). There were no differences in changes in total or bout MVPA. However, those with very poor fitness had lower bout MVPA at baseline vs. those with poor or better fitness (16±20 vs 33±31 min/d, p=0.03). At 18 months, both groups increased bout MVPA, however bout MVPA remained lower in the very poor vs. poor or better group (24±29 vs 42±29 min/d, p=0.03). Total MVPA showed a similar pattern. CONCLUSION: Baseline fitness may moderate 18-month weight loss, as those with very poor fitness lost less weight compared to those with poor or better fitness levels. Those with poor or better fitness at baseline achieved significantly higher mean levels of MVPA at 18 months compared to those with very poor fitness. Participants with very poor fitness at baseline may require additional exercise support during a BWLP to achieve the high levels of MVPA recommended for weight loss maintenance.

Study ObjectiveIdentify small molecule biomarkers of insufficient sleep using untargeted plasma metabolomics in humans undergoing experimental insufficient sleep.MethodsWe conducted a crossover laboratory study where 16 normal-weight participants (eight men; age 22 ± 5 years; body mass index < 25 kg/m2) completed three baseline days (9 hours sleep opportunity per night) followed by 5-day insufficient (5 hours sleep opportunity per night) and adequate (9 hours sleep opportunity per night) sleep conditions. Energy balanced diets were provided during baseline, with ad libitum energy intake provided during the insufficient and adequate sleep conditions. Untargeted plasma metabolomics analyses were performed using blood samples collected every 4 hours across the final 24 hours of each condition. Biomarker models were developed using logistic regression and linear support vector machine (SVM) algorithms.ResultsThe top-performing biomarker model was developed by linear SVM modeling, consisted of 65 compounds, and discriminated insufficient versus adequate sleep with 74% overall accuracy and a Matthew’s Correlation Coefficient of 0.39. The compounds in the top-performing biomarker model were associated with ATP Binding Cassette Transporters in Lipid Homeostasis, Phospholipid Metabolic Process, Plasma Lipoprotein Remodeling, and sphingolipid metabolism.ConclusionWe identified potential metabolomics-based biomarkers of insufficient sleep in humans. Although our current biomarkers require further development and validation using independent cohorts, they have potential to advance our understanding of the negative consequences of insufficient sleep, improve diagnosis of poor sleep health, and could eventually help identify targets for countermeasures designed to mitigate the negative health consequences of insufficient sleep.

Exercise provides a robust physiological stimulus that evokes cross-talk among multiple tissues that when repeated regularly (i.e., training) improves physiological capacity, benefits numerous organ systems, and decreases the risk for premature mortality. However, a gap remains in identifying the detailed molecular signals induced by exercise that benefits health and prevents disease. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to address this gap and generate a molecular map of exercise. Preclinical and clinical studies will examine the systemic effects of endurance and resistance exercise across a range of ages and fitness levels by molecular probing of multiple tissues before and after acute and chronic exercise. From this multi-omic and bioinformatic analysis, a molecular map of exercise will be established. Altogether, MoTrPAC will provide a public database that is expected to enhance our understanding of the health benefits of exercise and to provide insight into how physical activity mitigates disease.

Exercise is accepted as a method to improve weight loss maintenance; however, the mechanisms by which this occurs have yet to be elucidated. In this pilot study, 13 women with obesity underwent a structured weight loss program (goal 8%–10% weight loss) and were then randomized to either a 12-wk diet (n = 7) or an aerobic exercise training (n = 6) intervention aimed at maintaining weight loss. At baseline, post–weight loss, and following the weight loss maintenance interventions, measurements of appetite (hunger and satiety) and appetite-regulating hormones (leptin, ghrelin, peptide tyrosine tyrosine, and glucagon-like peptide 1) were obtained after an overnight fast and for 3 h after a standardized test meal. Ad libitum energy intake was measured at a lunch meal. During the weight loss phase, participants lost 9.1% ± 1.1% of baseline body weight. Participants in both groups maintained weight loss during the 12-wk weight loss maintenance intervention. No differences in fasting leptin (P = 0.68) or in ghrelin (P = 0.30), peptide tyrosine tyrosine (P = 0.93), and glucagon-like peptide 1 (P = 0.98) area under the curve were detected between groups. Similarly, ratings of hunger (P = 0.99) and satiety (P = 0.65) area under the curve after the standardized test meal also did not differ between the groups nor did ad libitum energy intake at lunch. In summary, the 12-wk diet and exercise interventions were equally effective at maintaining weight loss in women, and no differences in measures of appetite regulation and food intake were found.

Background Physical activity remains low and nearly unchanged from preoperative levels following total knee arthroplasty (TKA), and this is thought to underlie long-term functional limitations, secondary health problems, and higher health care costs after TKA. Objective Our objective is to determine whether a telehealth-based intervention could improve physical activity and functional outcomes after TKA. Design The design is a 2-arm, parallel, assessor-blinded, randomized controlled trial with baseline, midintervention, postintervention, and 6-month follow-up assessments. Setting The setting is one academic medical center and one Veterans Affairs health care system. Participants One hundred US military veterans (aged 50–85 years) scheduled for unilateral TKA will participate in this study. Intervention The telehealth-based intervention to change physical activity behavior will be delivered through 10 sessions each of 30 minutes over a 12-week period. Participants will be provided with a wearable physical activity monitor to receive feedback on step count and guide goal-setting. Control participants will receive telehealth-based education on nonbehavioral aspects of health for the same frequency and duration as the intervention group. For both groups, telehealth sessions will occur concurrently with standardized outpatient rehabilitation. Measurements The primary outcome will be change in physical activity, assessed as daily step counts measured using an accelerometer-based sensor. Secondary outcomes will be measured using the Life-Space Assessment questionnaire and change in physical function (30-Second Chair-Stand Test, Timed “Up & Go” Test, Six-Minute Walk Test, Western Ontario and McMaster Universities Osteoarthritis Index, and Veterans RAND 12-Item Health Survey). Limitations Participant and interventionist blinding is not possible. Conclusions This trial will assess the efficacy of a novel behavior-change intervention to improve physical activity and physical function in patients after TKA. Effective physical activity behavior change could provide clinicians with a technique to augment current practice and resolve poor physical activity outcomes, long-term health problems, and high costs following TKA.

Reducing estrogen in women results in decreases in energy expenditure, but the mechanism(s) remain largely unknown. We postulate that the loss of estrogens in women is associated with increased accumulation of bone marrow (BM)-derived adipocytes in white adipose tissue, decreased activity of brown adipose tissue, and reduced levels of physical activity. Regular exercise may counteract the effects of estrogen deficiency.

PURPOSE: To determine the effects of 5 months of ovarian hormone suppression in pre-menopausal women on objectively measured physical activity (PA). METHODS: Participants (age = 35±8 yr; body mass index = 27±6 kg·m(−2)) received monthly intramuscular injections of gonadotropin releasing hormone agonist therapy (GnRH(AG)) which suppresses pituitary gonadotropins and results in suppression of ovarian sex hormones. Women were randomized to receive concurrent transdermal E(2) (GnRH(AG)+E(2); n=30) or placebo (GnRH(AG)+PL, n=31). PA was assessed for 1 week before and during each month of the 5-month intervention using a hip-worn accelerometer (Actical, Mini Mitter Co., Inc., Bend, OR). Estimates of time spent in sedentary, light, and moderate-to-vigorous physical activity (MVPA) were derived using a previously published equation. Subsets of participants in each group were also randomized to a supervised progressive resistance exercise training program. RESULTS: Total MVPA tended towards being higher (p=0.08) in the GnRH(AG)+E(2) group at month 4. There were no significant effects of intervention or time in sedentary or light PA. In the subset of women who did not participate in structured exercise training for which Actical data were obtained (N=16 in each group), total MVPA was higher at month 4 (p=0.01). CONCLUSION: Physical activity levels appear to be maintained at a higher level in women undergoing pharmacological suppression of ovarian function with E(2) add back when compared with women treated with placebo. These data provide proof of concept data that E(2) contributes to the regulation of PA in humans. However, given the exploratory nature of this study, future confirmatory investigations will be necessary.

Purpose To compare energy intake (EI) and appetite regulation responses between men and women following acute bouts of aerobic (AEx), resistance exercise (REx), and a sedentary control (CON). Methods Men and women (n = 24; 50% male) with overweight/obesity, matched on age (32.3 ± 2 vs. 36.8 ± 2 yrs, p = 0.14) and BMI (28.1 ± 1.2 vs 29.0 ± 1.5 kg/m2, p = 0.64) completed 3 conditions: 1) AEx (65–70% of age-predicted maximum heart rate for 45 min); 2) REx (1-set to failure on 12 exercises); and 3) CON. Each condition was initiated in the post-prandial state (35 min following consumption of a standardized breakfast). Appetite (visual analog scale for hunger, satiety, and prospective food consumption [PFC]) and hormones (ghrelin, PYY, and GLP-1) were measured in the fasted state and every 30 min post-prandially for 3 h. Post-exercise ad libitum EI at the lunch meal was also measured. Results Men reported higher levels of hunger compared to women across all study conditions (AEx: Men: 7815.00 ± 368.3; Women: 5428.50 ± 440.0 mm x 180 min; p = 0.025; REx: Men: 7110.00 ± 548.4; Women: 6086.25 ± 482.9 mm x 180 min; p = 0.427; CON: Men: 8315.00 ± 429.8; Women: 5311.25 ± 543.1 mm x 180 min; p = 0.021) and consumed a greater absolute caloric load than women at the ad libitum lunch meal (AEx: Men: 1021.6 ± 105.4; Women: 851.7 ± 70.5 kcals; p = 0.20; REx: Men: 1114.7 ± 104.0; Women: 867.7 ± 76.4 kcals; p = 0.07; CON: Men: 1087.0 ± 98.8; Women: 800.5 ± 102.3 kcals; p = 0.06). However, when adjusted for relative energy needs, there was no difference in relative ad libitum EI observed between men and women. No differences in Area Under the Curve for Satiety, PFC, ghrelin, PYY, and GLP-1 were noted between men and women following acute exercise (all p > 0.05). Conclusions These data suggest that women report lower ratings of appetite following an acute bout of exercise or sedentary time when compared to men, yet have similar relative EI. Future work is needed to examine whether sex-based differences in appetite regulation and EI are present with chronic exercise of differing modalities.

Objective The objective of this study was to compare patterns of objectively measured moderate-to-vigorous physical activity (MVPA, ≥ 3.00 metabolic equivalents [METs]), light-intensity physical activity (LPA, 1.50-2.99 METs), and sedentary behavior (SB

Objective ambulatory activity during daily living has not been characterized for people with Parkinson disease prior to initiation of dopaminergic medication. Our goal was to characterize ambulatory activity based on average daily step count and examine determinants of step count in nonexercising people with de novo Parkinson disease.We analyzed baseline data from a randomized controlled trial, which excluded people performing regular endurance exercise. Of 128 eligible participants (mean ± SD = 64.3 ± 8.6 years), 113 had complete accelerometer data, which were used to determine daily step count. Multiple linear regression was used to identify factors associated with average daily step count over 10 days. Candidate explanatory variable categories were (1) demographics/anthropometrics, (2) Parkinson disease characteristics, (3) motor symptom severity, (4) nonmotor and behavioral characteristics, (5) comorbidities, and (6) cardiorespiratory fitness.Average daily step count was 5362 ± 2890 steps per day. Five factors explained 24% of daily step count variability, with higher step count associated with higher cardiorespiratory fitness (10%), no fear/worry of falling (5%), lower motor severity examination score (4%), more recent time since Parkinson disease diagnosis (3%), and the presence of a cardiovascular condition (2%).Daily step count in nonexercising people recruited for this intervention trial with de novo Parkinson disease approached sedentary lifestyle levels. Further study is warranted for elucidating factors explaining ambulatory activity, particularly cardiorespiratory fitness, and fear/worry of falling. Clinicians should consider the costs and benefits of exercise and activity behavior interventions immediately after diagnosis of Parkinson disease to attenuate the health consequences of low daily step count.Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A170).

It is widely assumed that structured exercise causes an additive increase in physical activity energy expenditure (PAEE) and total daily energy expenditure (TDEE). However, the common observation that exercise often leads to a less than expected decrease in body weight, without changes in energy intake, suggests that some compensatory behavioral adaptations occur. A small number of human studies have shown that adoption of structured exercise can lead to decreases in PAEE, which is often interpreted as a decrease in physical activity (PA) behavior. An even smaller number of studies have objectively measured PA, and with inconsistent results. In animals, high levels of imposed PA induce compensatory changes in some components of TDEE. Recent human cohort studies also provide evidence that in those at the highest levels of PA, TDEE is similar when compared to less physically active groups. The objective of this review is to summarize the effects of structured exercise training on PA, sedentary behavior, PAEE and TDEE. Using models from ecological studies in animals and observational data in humans, an alternative model of TDEE in humans is proposed. This model may serve as a framework to investigate the complex and dynamic regulation of human energy budgets.

Objective This study aimed to evaluate the impact of timing of exercise initiation on weight loss within a behavioral weight loss program. Methods Adults with overweight or obesity (N = 170; age 18-55 years; BMI 25-42 kg/m2 ; 83.5% women) were enrolled in an 18-month behavioral weight loss program consisting of a reduced-calorie diet, exercise, and group-based support. The standard group (STD) received a supervised exercise program (progressing to 300 min/wk of moderate-intensity aerobic exercise) during months 0 to 6. The sequential group (SEQ) was asked to refrain from changing exercise during months 0 to 6 and received the supervised exercise program during months 7 to 12. On completion of supervised exercise, both groups were instructed to continue 300 min/wk of moderate-intensity exercise for the study duration. Results At 6 months, the STD group exhibited greater reductions in body weight (-8.7 ± 0.7 kg) compared with the SEQ group (-6.9 ± 0.6 kg; P = 0.047). Between 6 and 18 months, the STD group regained more weight (2.5 ± 0.8 kg vs. 0.0 ± 0.8 kg; P = 0.02). At 18 months, there were no between-group differences in changes in weight (STD: -6.9 ± 1.2 kg; SEQ: -7.9 ± 1.2 kg), fat mass, lean mass, physical activity, or attrition. Conclusions Both immediate and delayed exercise initiation within a behavioral weight loss program resulted in clinically meaningful weight loss at 18 months. Thus, timing of exercise initiation can be personalized based on patient preference.

Insufficient sleep induces insulin resistance and is associated with an increased risk for developing obesity and cardiometabolic diseases, implicating sleep loss as a metabolic stressor. Fibroblas...

AB We have previously shown that motor-driven (passive) stationary cycling elevates energy expenditure (EE). Purpose: This study aimed to quantify how acute passive cycling affects glucose and insulin responses to an oral glucose tolerance test (OGTT) and basic cognition compared with sitting and moderate-intensity active cycling. Methods: Twenty-four physically inactive healthy males completed three trials in randomized order involving 30-min conditions of sitting, passive cycling, and moderate-intensity cycling. During each condition, EE was measured, and participants performed cognitive tests. After each condition, a 2-h OGTT was performed. Results: EE was significantly higher during the cycling conditions compared with sitting (1.36 +/- 0.58 and 6.50 +/- 1.73 kcal[middle dot]min-1 greater than sitting for passive and moderate-intensity, respectively). A significant correlation was found between body fat percentage and postsitting OGTT 2-h postplasma glucose (r2 = 0.30, P < 0.05); thus, participants were divided into lean (n = 11) and nonlean (n = 13) groups. In the nonlean group, compared with sitting, passive cycling lowered 2-h postplasma glucose (7.7 +/- 1.3 vs 6.9 +/- 1.6 mmol[middle dot]L-1, respectively, P < 0.05), and the Matsuda whole-body insulin sensitivity index (WBISI) was higher (2.74 +/- 0.86 vs 3.36 +/- 1.08, P < 0.05). In addition, passive and moderate-intensity cycling had similar beneficial effects on 2-h postplasma glucose and WBISI. Cognitive performance did not significantly differ between the sitting and passive cycling conditions. Conclusions: Two-hour postplasma glucose was lower and WBISI after acute passive cycling was higher in nonlean participants. Given that and the increase in EE without changes in cognitive performance, we propose passive cycling as a promising intervention to counteract some of the deleterious effects of prolonged sitting in the workplace. (C) 2016 American College of Sports Medicine

Objective To evaluate the safety and tolerability of alternate-day fasting (ADF) and to compare changes in weight, body composition, lipids, and insulin sensitivity index (Si) with those produced by a standard weight loss diet, moderate daily caloric restriction (CR). Methods Adults with obesity (BMI ≥30 kg/m2, age 18-55) were randomized to either zero-calorie ADF (n = 14) or CR (−400 kcal/day, n = 12) for 8 weeks. Outcomes were measured at the end of the 8-week intervention and after 24 weeks of unsupervised follow-up. Results No adverse effects were attributed to ADF, and 93% completed the 8-week ADF protocol. At 8 weeks, ADF achieved a 376 kcal/day greater energy deficit; however, there were no significant between-group differences in change in weight (mean ± SE; ADF −8.2 ± 0.9 kg, CR −7.1 ± 1.0 kg), body composition, lipids, or Si. After 24 weeks of unsupervised follow-up, there were no significant differences in weight regain; however, changes from baseline in % fat mass and lean mass were more favorable in ADF. Conclusions ADF is a safe and tolerable approach to weight loss. ADF produced similar changes in weight, body composition, lipids, and Si at 8 weeks and did not appear to increase risk for weight regain 24 weeks after completing the intervention.

Understanding how exercise affects communication across the brain in overweight/obese individuals may provide insight into mechanisms of weight loss and maintenance. In the current study, we examined the effects of a 6-month exercise program in 11 overweight/obese individuals (mean BMI: 33.6±1.4 mg/kg2; mean age: 38.2±3.2 years) on integrative brain “hubs,” which are areas with high levels of connectivity to multiple large-scale networks thought to play an important role in multimodal integration among brain regions. These integrative hubs were identified with a recently developed between-network connectivity (BNC) metric, using functional magnetic resonance imaging (fMRI). BNC utilizes a multiple regression analysis approach to assess relationships between the time series of large-scale functionally-connected brain networks (identified using independent components analysis) and the time series of each individual voxel in the brain. This approach identifies brain regions with high between-network interaction, i.e., areas with high levels of connectivity to many large-scale networks. Changes in BNC following exercise were determined using paired t-tests, with results considered significant at a whole-brain level if they exceeded a voxel-wise threshold of p < 0.01 and cluster-level family-wise error (FWE) correction for multiple comparisons of p < 0.05. Following the intervention, BNC in the posterior cingulate cortex (PCC) was significantly reduced (p < 0.001). The changes driving the observed effects were explored using Granger causality, finding significant reductions in both outgoing causal flow from the PCC to a number of networks (p < 0.05; language network, visual network, sensorimotor network, left executive control network, basal ganglia network, posterior default mode network), in addition to reductions in ingoing causal flow to the PCC from a number of networks (p < 0.05; ventral default mode network, language network, sensorimotor network, basal ganglia network). Change in BNC was related to changes in aerobic fitness level (VO2 max; p = 0.008) and perceived hunger (Three Factor Eating Questionnaire; p = 0.040). Overall, the impact of exercise on communication between large-scale networks may contribute to individual responsivity to exercise.

Background/objectives Circadian physiology has been linked to body weight regulation and obesity. To date, few studies have assessed the association between exercise timing and weight related outcomes. The aim of this secondary analysis was to explore the impact of exercise timing (i.e., 24 h clock time of exercise session) on weight loss and components of energy balance. Subjects/methods Overweight/obese (BMI 25.0–39.9 kg/m2), physically inactive, young adults (~51% female) completed a 10-month supervised exercise program (400 or 600 kcal/session for 5 days/week) or served as non-exercise controls (CON). Participants were categorized based on the time of day in which they completed exercise sessions (Early-Ex: >50% of sessions completed between 7:00 and 11:59 am; (n = 21), Late-Ex: >50% of sessions completed between 3:00 and 7:00 pm; (n = 25), Sporadic-Ex: n = 24), and CON; (n = 18)). Body weight, energy intake (EI; digital photography), and non-exercise physical activity (NEPA; accelerometer) were assessed at baseline, 3.5, 7, and 10 months. Total daily energy expenditure (TDEE; doubly labeled water), was assessed at baseline and 10 months. Results At month 10, weight loss was significantly greater in both Early-EX (−7.2 ± 1.2%; p p = 0.01) vs CON (+0.5 ± 1.0%), and Early-EX vs Late-EX (−2.1 ± 1.0%; p P > 0.05). A significant group × time interaction (p = 0.02) was observed for NEPA (counts/min), however, after adjusting for multiple comparisons, group effects were no longer significant. Conclusions Despite minimal differences in components of energy balance, Early-EX lost significantly more weight compared with Late-Ex. Although the mechanisms are unclear, the timing of exercise may be important for body weight regulation.

Study Objectives To evaluate the associations between sedentary time, total (total-PA), light (light-PA), moderate (MOD-PA), and vigorous (VIG-PA) physical activity with indices of sleep in postmenopausal women. Methods Baseline self-reported data from the Women’s Health Initiative Observational Study (n = 75 074) were used in this cross-sectional analysis. Total-PA, light-PA, MOD-PA, and VIG-PA were categorized by metabolic equivalents of the activity (MET-hour [hr]/week [wk]) and were estimated using validated questionnaires. Sedentary time was categorized by hr/day and was estimated via questionnaire. Logistic regression was used to examine the associations between these variables and short sleep (≤6 hr/night), long sleep (≥10 hr/night), poor sleep quality, and insomnia symptoms after adjustment for age, race, socioeconomic status, body mass index, health status, depressive symptoms, smoking status, alcohol use, hormone therapy, and comorbidities. Results Higher sedentary time (>11 hr/day) was associated with higher odds of short sleep (odds ratio [OR] = 1.80, 95% confidence interval [CI]: 1.72–1.88), poor sleep quality (OR = 1.85, 95% CI: 1.74–1.97), and insomnia symptoms (OR = 1.56, 95% CI: 1.49–1.64). Light-PA (>0 MET-hr/wk) was associated with lower odds of short sleep (OR = 0.96, 95% CI: 0.92–1.00), and higher amounts of total-PA (OR = 0.90, 95% CI: 0.84–0.97), light-PA (OR = 0.94, 95% CI: 0.89–1.00), and MOD-PA (OR = 0.91, 95% CI: 0.86–0.97) were associated with lower odds of poor sleep quality. Conclusions Our findings suggest that higher levels of light and moderate intensity physical activity are associated with better sleep quality, whereas higher amounts of sedentary time are associated with short sleep and lower quality sleep. Future studies should investigate the directionality of these associations and potential causal pathways.

Free fatty acids (FFA) are a primary fuel source for heart and skeletal muscle, particularly during fasting. In addition, both high fat feeding and insufficient sleep have been shown to increase nocturnal FFA in animal and human models, respectively. However, findings from studies of insufficient sleep have been limited by a focus on male subjects. Furthermore, the impact of ad libitum food intake during insufficient sleep on FFA has not been examined. We therefore examined potential sex differences in circulating 24-hour FFA profiles during habitual sleep and insufficient sleep under ad libitum feeding conditions. Healthy adults (7 females: 23.6±3.2 y, BMI 22.1±1.1 kg/m2; 7 males: 25.7±4.6 y, BMI 22.5±1.2 kg/m2; mean±SD) were studied after five inpatient days consisting of 9h scheduled sleep per night at habitual bedtime and five inpatient days consisting of 5h scheduled sleep beginning 2 hours later than habitual bedtime in a crossover design. On the 5th day in each condition, blood was sampled hourly beginning one hour after scheduled wake-time for 24 hours. In both conditions, participants were provided 3 scheduled meals and 2 snacks designed to provide approximately 130-150% of energy requirements, and had free access to snacks during scheduled waketime. Females showed a more robust FFA response to food intake during both habitual and insufficient sleep vs. men, likely due to positive energy balance for men in both conditions. In addition, both men and women displayed altered FFA patterns during insufficient sleep such that the nocturnal peak was later in the 24hour profile. We provide evidence of sex differences in 24-hour FFA profiles in response to overeating with and without insufficient sleep. The significance of these differences and how they may affect responses to sleep and/or metabolic perturbations is unknown. Future studies are necessary to determine whether differences in FFA may lead to sex differences in metabolic impairments in response to insufficient sleep. Disclosure J.L. Broussard: None. C.M. Depner: None. R. Markwald: None. R.H. Eckel: Advisory Panel; Self; Novo Nordisk Inc., Merck & Co., Inc. L. Perreault: Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S. Advisory Panel; Self; Merck & Co., Inc.. Speaker's Bureau; Self; Merck & Co., Inc., AstraZeneca, Janssen Pharmaceuticals, Inc., Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; Sanofi. J. Higgins: None. E. Melanson: None. K. Wright: Research Support; Self; Philips Respironics, CurAegis Technologies, Inc., Somalogics, National Institutes of Health, Pac-12, Office of Naval Research. Consultant; Self; National Heart, Lung, and Blood Institute, CurAegis Technologies, Inc., Circadian Therapeutics, LTD. Board Member; Self; Sleep Research Society. Consultant; Self; American Academy of Sleep Medicine, American Diabetes Association, American College of Chest Physicians.

Older adults do not get enough physical activity increasing risk for chronic disease and loss of physical function. The purpose of this study was to determine whether neuromuscular, metabolic, and cardiorespiratory indicators of walking effort explain daily activity in community-dwelling older adults. Sixteen women and fourteen men, 78 ± 8 years, performed a steady-state walk on a treadmill at 1.25 m s−1 while muscle activation, heart rate, lactate, respiratory exchange ratio, oxygen consumption (VO2), ventilation, and rating of perceived exertion (RPE) were recorded as markers of Walking Effort. Daily walking time, sitting/lying time, energy expenditure, and up-down transitions were recorded by accelerometers as markers of Daily Activity. Structural equation modeling was used to explore the relationship between the latent variables Walking Effort and Daily Activity controlling for age and BMI. Participants spent 9.4 ± 1.9 h of the waking day sedentary and 1.9 ± 0.6 h walking. In the structural equation model, the latent variable Walking Effort explained 64% of the variance in the Daily Activity latent variable (β = 0.80, p = 0.004). Walking Effort was identified by heart rate (β = 0.64), ventilation (β = 0.88), vastus lateralis activation (β = 0.49), and lactate (β = 0.58), all p

Daytime light exposure has been reported to impact or have no influence on energy metabolism in humans. Further, whether inter-individual differences in wake, sleep, 24 h energy expenditure, and RQ during circadian entrainment and circadian misalignment are stable across repeated 24 h assessments is largely unknown. We present data from two studies: Study 1 of 15 participants (7 females) exposed to three light exposure conditions: continuous typical room ~100 lx warm white light, continuous ~750 lx warm white light, and alternating hourly ~750 lx warm white and blue-enriched white light on three separate days in a randomized order; and Study 2 of 14 participants (8 females) during circadian misalignment induced by a simulated night shift protocol. Participants were healthy, free of medical disorders, medications, and illicit drugs. Participants maintained a consistent 8 h per night sleep schedule for one week as an outpatient prior to the study verified by wrist actigraphy, sleep diaries, and call-ins to a time stamped recorder. Participants consumed an outpatient energy balance research diet for three days prior to the study. The inpatient protocol for both studies consisted of an initial sleep disorder screening night. For study 1, this was followed by three standard days with 16 h scheduled wakefulness and 8 h scheduled nighttime sleep. For Study 2, it was followed by 16 h scheduled wake and 8 h scheduled sleep at habitual bedtime followed by three night shifts with 8 h scheduled daytime sleep. Energy expenditure was measured using whole-room indirect calorimetry. Constant posture bedrest conditions were maintained to control for energy expenditure associated with activity and the baseline energy balance diet was continued with the same exact meals across days to control for thermic effects of food. No significant impact of light exposure was observed on metabolic outcomes in response to daytime light exposure. Inter-individual variability in energy expenditure was systematic and ranged from substantial to almost perfect consistency during both nighttime sleep and circadian misalignment. Findings show robust and stable trait-like individual differences in whole body 24 h, waking, and sleep energy expenditure, 24 h respiratory quotient—an index of a fat and carbohydrate oxidation—during repeated assessments under entrained conditions, and also in 24 h and sleep energy expenditure during repeated days of circadian misalignment. Keywords: Shift work, Biological day, Biological night

Parkinson disease is a progressive neurologic disorder. Limited evidence suggests endurance exercise modifies disease severity, particularly high-intensity exercise.To examine the feasibility and safety of high-intensity treadmill exercise in patients with de novo Parkinson disease who are not taking medication and whether the effect on motor symptoms warrants a phase 3 trial.The Study in Parkinson Disease of Exercise (SPARX) was a phase 2, multicenter randomized clinical trial with 3 groups and masked assessors. Individuals from outpatient and community-based clinics were enrolled from May 1, 2012, through November 30, 2015, with the primary end point at 6 months. Individuals with idiopathic Parkinson disease (Hoehn and Yahr stages 1 or 2) aged 40 to 80 years within 5 years of diagnosis who were not exercising at moderate intensity greater than 3 times per week and not expected to need dopaminergic medication within 6 months participated in this study. A total of 384 volunteers were screened by telephone; 128 were randomly assigned to 1 of 3 groups (high-intensity exercise, moderate-intensity exercise, or control).High-intensity treadmill exercise (4 days per week, 80%-85% maximum heart rate [n = 43]), moderate-intensity treadmill exercise (4 days per week, 60%-65% maximum heart rate [n = 45]), or wait-list control (n = 40) for 6 months.Feasibility measures were adherence to prescribed heart rate and exercise frequency of 3 days per week and safety. The clinical outcome was 6-month change in Unified Parkinson's Disease Rating Scale motor score.A total of 128 patients were included in the study (mean [SD] age, 64 [9] years; age range, 40-80 years; 73 [57.0%] male; and 108 [84.4%] non-Hispanic white). Exercise rates were 2.8 (95% CI, 2.4-3.2) days per week at 80.2% (95% CI, 78.8%-81.7%) maximum heart rate in the high-intensity group and 3.2 (95% CI, 2.8-3.6; P = .13) days per week at 65.9% (95% CI, 64.2%-67.7%) maximum heart rate in the moderate-intensity group (P .001). The mean change in Unified Parkinson's Disease Rating Scale motor score in the high-intensity group was 0.3 (95% CI, -1.7 to 2.3) compared with 3.2 (95% CI, 1.4 to 5.1) in the usual care group (P = .03). The high-intensity group, but not the moderate-intensity group, reached the predefined nonfutility threshold compared with the control group. Anticipated adverse musculoskeletal events were not severe.High-intensity treadmill exercise may be feasible and prescribed safely for patients with Parkinson disease. An efficacy trial is warranted to determine whether high-intensity treadmill exercise produces meaningful clinical benefits in de novo Parkinson disease.clinicaltrials.gov Identifier: NCT01506479.

Suppressing sex hormones in women for 1 wk reduces resting energy expenditure (REE). The effects of more chronic suppression on REE and other components of total energy expenditure (TEE), and whether the reduction in REE is specifically due to loss of estradiol (E2), are not known. We compared the effects of 5 mo of sex hormone suppression (gonadotropin releasing hormone agonist therapy, GnRHAG) with placebo (PL) or E2 add-back therapy on REE and the components of TEE. Premenopausal women received GnRHAG (leuprolide acetate 3.75 mg/mo) and were randomized to receive transdermal therapy that was either E2 (0.075 mg/d; n = 24; means ± SD, aged = 37 ± 8 yr, BMI = 27.3 ± 6.2 kg/m2) or placebo ( n = 21; aged = 34 ± 9 yr, BMI = 26.8 ± 6.2 kg/m2). REE was measured by using a metabolic cart, and TEE, sleep EE (SEE), exercise EE (ExEE, 2 × 30 min bench stepping), non-Ex EE (NExEE), and the thermic effect of feeding (TEF) were measured by using whole room indirect calorimetry. REE decreased in GnRHAG+PL [mean (95% CI), −54 (−98, −15) kcal/d], but not GnRHAG+E2 [+6 (−33, +45) kcal/d] (difference in between-group changes, P < 0.05). TEE decreased in GnRHAG+PL [−128 (−214, −41) kcal/d] and GnRHAG+E2 [−96 (−159, −32) kcal/d], with no significant difference in between-group changes ( P = 0.55). SEE decreased similarly in both GnRHAG+PL [−0.07 (−0.12, −0.03) kcal/min] and GnRHAG+E2 [−0.07 (−0.12, −0.02) kcal/min]. ExEE decreased in GnRHAG+PL [−0.46 (−0.79, −0.13) kcal/min], but not GnRHAG+E2 [−0.30 (−0.65, +0.06) kcal/min]. There were no changes in TEF or NExEE in either group. In summary, chronic pharmacologic suppression of sex hormones reduced REE and this was prevented by E2 therapy.

Short sleep duration and circadian misalignment are hypothesized to causally contribute to health problems including obesity, diabetes, metabolic syndrome, heart disease, mood disorders, cognitive impairment, and accidents. Here, we investigated the influence of morning circadian misalignment induced by an imposed short nighttime sleep schedule on impaired insulin sensitivity, a precursor to diabetes. Imposed short sleep duration resulted in morning wakefulness occurring during the biological night (i.e., circadian misalignment)-a time when endogenous melatonin levels were still high indicating the internal circadian clock was still promoting sleep and related functions. We show the longer melatonin levels remained high after wake time, insulin sensitivity worsened. Overall, we find a simulated 5-day work week of 5-hr-per-night sleep opportunities and ad libitum food intake resulted in ∼20% reduced oral and intravenous insulin sensitivity in otherwise healthy men and women. Reduced insulin sensitivity was compensated by an increased insulin response to glucose, which may reflect an initial physiological adaptation to maintain normal blood sugar levels during sleep loss. Furthermore, we find that transitioning from the imposed short sleep schedule to 9-hr sleep opportunities for 3 days restored oral insulin sensitivity to baseline, but 5 days with 9-hr sleep opportunities was insufficient to restore intravenous insulin sensitivity to baseline. These findings indicate morning wakefulness and eating during the biological night is a novel mechanism by which short sleep duration contributes to metabolic dysregulation and suggests food intake during the biological night may contribute to other health problems associated with short sleep duration.

Introduction: We compared fatigability and activation of elbow flexor muscles in children at 3 pubertal stages during a sustained submaximal contraction. Methods: In 72 healthy children (39 boys) aged 11 ± 3 years (range, 8–14 years), differences in fatigability (time to task failure) and muscle activation were compared at 3 Tanner stages (T1–T3). Results: Time to task failure and muscle activation were similar between boys and girls at prepubertal Tanner stage 1. Time to task failure was briefer for girls than boys at Tanner stages 2 and 3 and was predicted by the coactivation indices and percent body fat in girls. Muscle torque was the only predictor for the time to task failure in boys. Conclusions: Differences in fatigability and muscle coactivation were evident during the initial pubertal stages (T2 and T3), but not before the onset of puberty (T1). Muscle Nerve 49: 887–894, 2014

DANNECKER, K. L., N. A. SAZONOVA, E. L. MELANSON, E. S. SAZONOV, and R. C. BROWNING. A Comparison of Energy Expenditure Estimation of Several Physical Activity Monitors. Med. Sci. Sports Exerc., Vol. 45, No. 11, pp. 2105–2112, 2013. Introduction: Accurately and precisely estimating free-living energy expenditure (EE) is important for monitoring energy balance and quantifying physical activity. Recently, single and multisensor devices have been developed that can classify physical activities, potentially resulting in improved estimates of EE. Purpose: This study aimed to determine the validity of EE estimation of a footwear-based physical activity monitor and to compare this validity against a variety of research and consumer physical activity monitors. Methods: Nineteen healthy young adults (10 men, 9 women) completed a 4-h stay in a room calorimeter. Participants wore a footwear-based physical activity monitor as well as Actical, ActiGraph, IDEEA, DirectLife, and Fitbit devices. Each individual performed a series of postures/activities. We developed models to estimate EE from the footwear-based device, and we used the manufacturer’s software to estimate EE for all other devices. Results: Estimated EE using the shoe-based device was not significantly different than measured EE (mean T SE; 476 T 20 vs 478 T 18 kcal, respectively) and had a root-mean-square error of 29.6 kcal (6.2%). The IDEEA and the DirectLlife estimates of EE were not significantly different than the measured EE, but the ActiGraph and the Fitbit devices significantly underestimated EE. Root-mean-square errors were 93.5 (19%), 62.1 kcal (14%), 88.2 kcal (18%), 136.6 kcal (27%), 130.1 kcal (26%), and 143.2 kcal (28%) for Actical, DirectLife, IDEEA, ActiGraph, and Fitbit, respectively. Conclusions: The shoe-based physical activity monitor provides a valid estimate of EE, whereas the other physical activity monitors tested have a wide range of validity when estimating EE. Our results also demonstrate that estimating EE based on classification of physical activities can be more accurate and precise than

Despite the common use of exercise as a weight loss strategy, little is known about its neuronal effects, and how these may be related to cognitive changes that impact food intake. The current study assessed the effects of a 6-month exercise intervention on intrinsic activity in the default mode network (DMN), a functionally connected network of brain regions including posterior cingulate cortex, cuneus/precuneus, medial prefrontal cortex, medial temporal lobe, and inferior parietal cortices, and salience network, which includes the anterior cingulate cortex and insula. Resting-state functional magnetic resonance imaging (fMRI) data were acquired in 12 overweight/obese individuals. The intervention was associated with a reduction in DMN activity in the precuneus (p=0.003, FWE-corrected), which was associated with greater fat mass loss (p=0.013) as well as reduced perceived hunger (Three Factor Eating Questionnaire, p=0.024) and hunger ratings in response to a meal (p=0.013). No changes were observed in the salience network in response to the exercise intervention. The association between DMN change and both fat mass loss and reduction of hunger ratings suggests that DMN function may be involved in the regulation of food intake behaviors. Given previous reports of DMN overactivity in overweight/obese individuals, the present findings may indicate an exercise-related “normalization” of network function.

Objective To compare the associations between neuromuscular performance and anthropometric characteristics with habitual levels of physical activity in boys and girls during the initial stages of puberty. Study design In a cross-sectional study of 72 healthy children (39 boys and 33 girls) ranging in age from 8 to 14 years, sex differences in anthropometric and motor performance characteristics were compared at 3 Tanner stages (T1-T3). Outcome variables included dual-energy x-ray absorptiometry measurements of body composition, assessments of neuromuscular function, and levels of physical activity (steps/day) measured by accelerometry. Results Physical activity was lower in girls than boys at T2 and T3, but there was no sex difference at T1. Physical activity increased with Tanner stage for boys but did not differ between Tanner stages in girls. Physical activity at each Tanner stage was strongly associated (R2 > 0.85) with neuromuscular characteristics for both boys and girls, but percentage of body fat also was associated with physical activity for T3 girls. Conclusions The attenuated gains in neuromuscular function experienced by girls in early stages of puberty were strongly associated with lower levels of physical activity, whereas the increase in physical activity exhibited by boys was mostly related to increases in the strength and endurance of leg muscles. Because sedentary activity is a known contributor to the development of obesity and type 2 diabetes in youth, this study helps to identify possible contributors to decreases in physical activity in young girls and provides potential targets for early intervention.

Increased physical activity is associated with successful long-term weight loss maintenance due to mechanisms likely more complex than simply increased energy expenditure. The impact of physical activity on the central regulation of food intake may be an important mechanism of this effect. The objective of this study was to examine the effects of exercise training and acute exercise on the neuronal response to food cues as well as eating behaviors. fMRI was performed in the fasted state at baseline and again after a 6 month progressive exercise intervention (supervised, 5 days/wk) both with and without an acute exercise bout in 12 overweight/obese (5 women, 7 men; BMI 33 ± 4 kg/m2) healthy adults. fMRI data were acquired while subjects were presented with visual stimuli of foods of high hedonic value as compared to neutral control objects. Questionnaires on eating behaviors, ratings of appeal and desire for foods, and ratings of appetite (hunger, satiety, prospective intake) using visual analog scales were also performed at baseline and again after the 6-month exercise intervention. While only a trend was observed for a reduction in body weight (102 ± 5 to 99 ± 6 kg, p = 0.09), a significant reduction in fat mass was observed (36.4 ± 2.8 to 33.7 ± 3.2 kg, p = 0.04), although as expected changes in fat mass were variable (− 10.0 to + 3.7 kg). Chronic exercise was associated with a reduction in the neuronal response to food, primarily in the posterior attention network and insula. A significant positive correlation between the change in fat/body mass and the change in insula response to food cues with chronic exercise was observed. An acute exercise bout attenuated the effects of chronic exercise. The exercise intervention, however, did not impact any of the measures of appetitive behavior. In summary, despite no effects on behavioral measures of appetite, chronic exercise training was associated with attenuation in the response to visual food cues in brain regions known to be important in food intake regulation. The insula, in particular, appears to play an important role in the potential exercise-induced weight loss and weight loss maintenance.

The impact of regular exercise on energy balance, fuel utilization, and nutrient availability, during weight regain was studied in obese rats, which had lost 17% of their weight by a calorie-restricted, low-fat diet. Weight reduced rats were maintained for 6 wk with and without regular treadmill exercise (1 h/day, 6 days/wk, 15 m/min). In vivo tracers and indirect calorimetry were then used in combination to examine nutrient metabolism during weight maintenance (in energy balance) and during the first day of relapse when allowed to eat ad libitum (relapse). An additional group of relapsing, sedentary rats were provided just enough calories to create the same positive energy imbalance as the relapsing, exercised rats. Exercise attenuated the energy imbalance by 50%, reducing appetite and increasing energy requirements. Expenditure increased beyond the energetic cost of the exercise bout, as exercised rats expended more energy to store the same nutrient excess in sedentary rats with the matched energy imbalance. Compared with sedentary rats with the same energy imbalance, exercised rats exhibited the trafficking of dietary fat toward oxidation and away from storage in adipose tissue, as well as a higher net retention of fuel via de novo lipogenesis in adipose tissue. These metabolic changes in relapse were preceded by an increase in the skeletal muscle expression of genes involved in lipid uptake, mobilization, and oxidation. Our observations reveal a favorable shift in fuel utilization with regular exercise that increases the energetic cost of storing excess nutrients during relapse and alterations in circulating nutrients that may affect appetite. The attenuation of the biological drive to regain weight, involving both central and peripheral aspects of energy homeostasis, may explain, in part, the utility of regular exercise in preventing weight regain after weight loss.

To explore whether nitrogen retention can differ on an isonitrogenous diet by changing when protein is consumed, we performed a short-term study in older individuals (64.5 ± 2.0 years) performing daily exercise while in energy balance. Participants consumed an isonitrogenous–isocaloric diet with the timing of a protein or carbohydrate beverage after exercise (protein after exercise [PRO], carbohydrate after exercise [CHO]) versus earlier in the day. Three-day mean energy balance (PRO: 202 ± 36 kcal and CHO: 191 ± 44 kcal; p = .68) did not differ between trials, but 3-day mean nitrogen balance was significantly more positive in the PRO (1.2 ± 0.32 g N) trial than the CHO trial (0.8 ± 0.45 g N; p < .05). Older individuals were better able to maintain nitrogen balance by simply changing when a portion of an identical amount of daily protein was consumed.