Walking net V ˙ O2 rises with advancing age in older women: where to go from here?

PURPOSE: Walking net V ˙ O2 tends to increase with advancing age; however, factors contributing to this relationship have not been widely described. The implications of such findings could inform targeted strategies to promote independent mobility in older adults. Herein, we evaluated the relationship between net V ˙ O2 and age at two submaximal workloads while exploring potential moderators of this relationship. METHODS: Secondary analyses were performed on 35 older (65 ± 3 years) women who completed a battery of physical assessments including fixed-speed, non-graded and graded (+ 2.5%) treadmill walking with indirect calorimetry to determine net V ˙ O2. Maximal oxygen uptake ( V ˙ O2max), knee extensor maximal isometric voluntary contraction (MVC), peak rate of torque development (RTD), and plantar flexor range-of-motion (PFROM) were also measured. RESULTS: Bivariate correlations showed non-graded (r = 0.403, p = 0.017) and graded (r = 0.413, p = 0.014) net V ˙ O2 were positively related to age. Notably, these relationships strengthened after adjusting for V ˙ O2max. Regression modeling showed age, RTD:MVC ratio (composite of muscle performance), and PFROM together explained 49% and 34% of the variance in non-graded and graded net V ˙ O2, respectively. Further analyses suggested knee extensor MVC moderates the relationship between non-graded net V ˙ O2 and age, accounting for 9% of the variance [ΔR2 = 0.090, F (1,31) = 4.13, p = 0.05]. CONCLUSION: These data support the premise that, in older women, walking net V ˙ O2 rises with advancing age, and additionally, the RTD:MVC ratio and PFROM are independent correlates of non-graded net V ˙ O2. Exercise interventions with a high degree of training specificity including explosive, velocity-based elements may promote independent mobility in older women.

Association between Fat-Free Mass Loss, Changes in Appetite, and Weight Regain in Individuals with Obesity.

BACKGROUND: The role of fat-free mass loss (FFML) in modulating weight regain in individuals with obesity, as well as the potential mechanisms involved, remain inconsistent. OBJECTIVES: The aim of this study was to determine if % FFML following weight loss (WL) is a predictor of weight regain and to investigate the association between %FFML and changes in appetite markers. METHODS: Seventy individuals with obesity (BMI: 36 ± 4 kg/m2; age: 44 ± 9 y; 29 males) underwent 8 wk of a very low energy diet (550-660 kcal/d), followed by 4 wk of gradual refeeding and weight stabilization and a 9-mo maintenance program (eucaloric diet). The primary outcomes were body weight and body composition (fat mass and fat-free mass). The secondary outcomes were plasma concentrations of ß-hydroxybutyrate (a marker of ketosis) in fasting and appetite-related hormones (ghrelin, glucagon-like peptide 1, peptide YY, and cholecystokinin) and subjective appetite feelings during fasting and every 30 min after a fixed breakfast for 2.5 h. All were measured at baseline, week 9, and 1 y [week 13 in 35 subjects (25 males)]. The association between FFML, weight regain, and changes in appetite was assessed by linear regression. RESULTS: WL at week 9 was 17.5 ± 4.3kg and %FFML 20.4 ± 10.6%. Weight regain at 1 y was 1.7 ± 8.2 kg (8.8 ± 45.0%). After adjusting for WL and fat mass at baseline, %FFML at week 9 was not a significant predictor of weight regain. Similar results were seen at week 13. The greater the %FFML at week 9, but not 13, the smaller the reduction, or greater the increase in basal ghrelin concentration (ß: -3.2; 95% CI: -5.0, -1.1; P = 0.003), even after adjusting for WL and ß-hydroxybutyrate. CONCLUSIONS: %FFML was not a significant predictor of weight regain at 1 y in individuals with obesity. However, a greater %FFML was accompanied by a greater increase in ghrelin secretion under ketogenic conditions, suggesting a link between fat-free mass and appetite regulation. This trial was registered at clinicaltrials.gov as NCT01834859.

Association between ß-Hydroxybutyrate Plasma Concentrations after Hypocaloric Ketogenic Diets and Changes in Body Composition.

BACKGROUND: Early studies show that ketogenic diets (KDs) lead to preferential loss of fat mass (FM), whereas preserving fat-free mass (FFM). Additionally, animal data support the anticatabolic effects of DL-3-hydroxybutyrate. From our knowledge, a potential association between ß-hydroxybutyrate (ßHB) plasma concentrations and changes in body composition has never been explored. OBJECTIVES: The main aim of this analysis was to determine if ßHB plasma concentrations, following hypocaloric KDs, were associated with FM and FFM changes in men and women with obesity. METHODS: Data from 199 individuals (BMI = 36.6 ± 4.3 kg/m2; age = 43.6 ± 9.8 y; 82 men) were collated from 3 weight loss studies employing common measures of body composition (air displacement plethysmography) and ßHB plasma concentration (ELISA). The association between ßHB and weight, FM and FFM loss (kg), and %FFM loss (%FFML) was investigated with Spearman correlation. Multivariable linear regression was used to determine if ßHB was a significant predictor of the changes in anthropometric variables, after adjusting for confounding factors. RESULTS: ßHB was not associated with FFML (% or kg), but a weak positive association was seen with FM loss (r = 0.182, P = 0.01, n = 199) and a trend with weight loss (r = 0.128, P = 0.072, n = 199). ßHB was a significant predictor of both weight and FM loss (kg), after adjusting for age, sex, baseline BMI, and intervention study. CONCLUSIONS: The magnitude of ketosis is not associated with FFM preservation. However, the higher the level of ketosis, the greater the weight and FM loss. Further studies are needed to confirm these findings and to explore the mechanisms involved. This trial was registered at clinicaltrials.gov identifier as NCT01834859, NCT04051190, NCT02944253.

Skeletal effects of eccentric strengthening exercise: a scoping review.

BACKGROUND: Conventional progressive concentric strengthening exercise (CSE) to improve bone mineral density (BMD) and bone mineral content (BMC) may not be feasible for populations with chronic musculoskeletal and/or metabolic conditions, such as osteoporosis or obesity. Muscle lengthening exercise, also known as an eccentric strengthening exercise (ESE), may have a special utility for those populations due to greater force generation versus CSE. In fact, greater mechanical loading can be induced on bone at lower resistance levels with ESE. However, effects of ESE on BMD and BMC are unclear. Thus, the purpose of this review was to interrogate the effects of ESE on BMD and BMC. METHODS: A literature review was conducted between January 1995 and April 2022 focusing on randomized controlled trials investigating the effects of ESE on BMD and/or BMC in humans. Terms covering the domains of exercise, bone, and populations were searched on PubMed, CINAHL, and Scopus. The methodological quality of each interventional study was rated using Physiotherapy Evidence Database (PEDro) scale. Cohen's d was calculated to determine the magnitude of the effects of ERE on site-specific outcome measures of BMD and/or BMC. RESULTS: Out of 1,182 articles initially found, a total of seven full length articles met our inclusion criteria. Of the seven studies, most of the interventions were performed in young (n = 5, PEDro = 5-7) versus middle-aged (n = 1, PEDro = 4) or older (n = 1, PEDro = 6) adults. BMD and BMC generally improved due to ESE; however the effects of ESE on BMD and BMC were non-homogenous. Effect size (d) ranged from 0.10-0.87 in young adults while it was 1.16 in older adults. Effect size (d) could not be calculated for the middle-aged adult study due to critical methodological limitations of the intervention. CONCLUSIONS: Large variability exists for the effectiveness of ESE on BMD/BMC across the human life spectrum. The benefits of ESE on BMD holds promise but rigorous studies are lacking. Further research is needed to examine if the dose, mode, age, and sex-specificity dictate effects of ESE on BMD/BMC.

ARTE index revisited: linking biomarkers of cardiometabolic health with free-living physical activity in postmenopausal women.

Activity-related energy expenditure (AEE) correlates with physical activity volume; however, between-person differences in body size and walking economy (net V̇o2) can influence AEE. The ratio of total energy expenditure (TEE) and resting energy expenditure (REE) estimates physical activity level (PAL) relative to body mass, yet does not account for variance in walking economy. The activity-related time equivalent (ARTEwalk) circumvents such constraints by adjusting for individual-specific walking economy. Herein, we compared AEE, PAL, and ARTEwalk index in a cohort (n = 81) of postmenopausal women while examining possible associations with biomarkers of cardiometabolic health. Secondary analyses were performed on postmenopausal women dichotomized above/below age group 50th percentile for body fat percent. TEE was reduced by 10% for the thermogenesis of digestion wherein AEE was calculated by subtracting REE from adjusted TEE. PAL was calculated as the ratio of TEE/REE. AEE was divided by the mean net energy expenditure of nongraded walking to calculate the ARTEwalk index. Between-group differences were not detected for AEE or PAL. However, the ARTEwalk index revealed that participants with less adiposity were more physically active (258 ± 149 vs. 198 ± 115 min·day-1; P = 0.046; g = 0.46). AEE and PAL did not correlate with cardiorespiratory fitness or biomarkers of cardiometabolic health. Cardiorespiratory fitness (r = 0.32), arterial elasticity (r = 0.24), total cholesterol/HDL-c ratio (r = -0.22), and body fat% (r = -0.24) were correlated with ARTEwalk. The ARTEwalk index may offer utility in detecting possible differences in physical activity volume among postmenopausal women and appears better associated with cardiometabolic biomarkers compared with AEE or PAL.

Stretch-Shortening Cycle Potentiation and Resistance Training-Induced Changes in Walking Economy/Ease and Activity-Related Energy Expenditure in Older Women.

ABSTRACT: Hunter, GR, Singh, H, Martins, C, Baranauskas, MN, and Carter, SJ. Stretch-shortening cycle potentiation and resistance training-induced changes in walking economy/ease and activity-related energy expenditure in older women. J Strength Cond Res 35(5): 1345-1349, 2021-Use of elastic energy to improve economy and ease of walking may be important for older adults. The purpose of this investigation was to determine whether baseline (i.e., untrained) stretch-shortening cycle potentiation (SSCP) was associated with potential changes in free-living activity-related energy expenditure (AEE) after supervised exercise training. Sedentary, postmenopausal women (n = 64) between 60 and 74 years of age were evaluated before and after 16 weeks of combined aerobic and resistance training. Assessments included: (a) body composition (dual-energy X-ray absorptiometry), (b) resting energy expenditure (indirect calorimetry), (c) submaximal and maximal walking (treadmill/indirect calorimetry), (d) total energy expenditure (doubly labeled water), and (e) one repetition maximum performed on an incline leg press and SSCP (calculated as the difference between concentric and countermovement leg press throw). Results indicated that baseline SSCP was related (r = -0.29; p < 0.02) to changes in AEE. However, subjects who possessed a high baseline SSCP did not increase SSCP or AEE, whereas subjects with low to moderate baseline SSCP demonstrated a significant increase in both SSCP (low +0.54 and moderate +0.47 m·s-1) and AEE (low +158 and moderate +333 kcal·d-1) post-training (all p less than 0.05). Our findings suggest that among subjects with low to moderate baseline SSCP, 16 weeks of combined aerobic and resistance training can increase SSCP and free-living AEE. However, subjects with high baseline SSCP may require tailored exercise to increase SSCP and possibly AEE.

Ratings of Perceived Exertion During Walking Predicts Endurance Independent of Physiological Effort in Older Women.

Hunter, GR, Neumeier, WH, Chandler-Laney, PC, Carter, SJ, Borges, JH, Hornbuckle, LM, Plaisance, EP, and Fisher, G. Ratings of perceived exertion during walking predicts endurance independent of physiological effort in older women. J Strength Cond Res 34(5): 1340-1344, 2020-This study aimed to determine whether ratings of perceived exertion (RPE) and physiological effort at different exercise intensities relate to exercise endurance. Ninety-eight sedentary women (older than 60 years) completed 3 submaximal locomotion tasks: (a) stair climbing, (b) flat walking at 2 mph, and (c) grade walking at 2 mph. Maximal treadmill endurance was measured at least 3 days before the submaximal tests. Oxygen uptake was measured during all tests, and RPE were collected for the submaximal tasks. Ratings of perceived exertion during moderate-intensity exercise (walking on the flat at 43% V[Combining Dot Above]O2max, partial R = -0.35, p < 0.01), but not higher intensity exercise (grade walk at 59% V[Combining Dot Above]O2max, p = 0.49, and stair climbing at 67% V[Combining Dot Above]O2max, p = 0.17), were related to endurance even after adjusting for aerobic capacity and physiological effort (composite of maximal heart rate, ventilation, and respiratory exchange ratio). However, physiological effort was significantly related to endurance for the higher intensity exercise (both grade walk and stair climbing partial R >-0.24, p < 0.02). Similar to previous findings that subjective ratings of fatigue at rest were related to RPE during low/moderate-intensity exercise, but not higher intensity exercise, these data further support Ekkekakis's dual-mode hypothesis that cognitive factors influence RPE during low/moderate-intensity exercise. A practical application is that the coach and personal trainer should know that physiological effort seems to play a greater role in influencing endurance than RPE as intensity of exercise increases.

Exercise plasma metabolomics and xenometabolomics in obese, sedentary, insulin-resistant women: impact of a fitness and weight loss intervention.

Insulin resistance has wide-ranging effects on metabolism, but there are knowledge gaps regarding the tissue origins of systemic metabolite patterns and how patterns are altered by fitness and metabolic health. To address these questions, plasma metabolite patterns were determined every 5 min during exercise (30 min, ∼45% of V̇o2peak, ∼63 W) and recovery in overnight-fasted sedentary, obese, insulin-resistant women under controlled conditions of diet and physical activity. We hypothesized that improved fitness and insulin sensitivity following a ∼14-wk training and weight loss intervention would lead to fixed workload plasma metabolomics signatures reflective of metabolic health and muscle metabolism. Pattern analysis over the first 15 min of exercise, regardless of pre- versus postintervention status, highlighted anticipated increases in fatty acid tissue uptake and oxidation (e.g., reduced long-chain fatty acids), diminution of nonoxidative fates of glucose [e.g., lowered sorbitol-pathway metabolites and glycerol-3-galactoside (possible glycerolipid synthesis metabolite)], and enhanced tissue amino acid use (e.g., drops in amino acids; modest increase in urea). A novel observation was that exercise significantly increased several xenometabolites ("non-self" molecules, from microbes or foods), including benzoic acid-salicylic acid-salicylaldehyde, hexadecanol-octadecanol-dodecanol, and chlorogenic acid. In addition, many nonannotated metabolites changed with exercise. Although exercise itself strongly impacted the global metabolome, there were surprisingly few intervention-associated differences despite marked improvements in insulin sensitivity, fitness, and adiposity. These results and previously reported plasma acylcarnitine profiles support the principle that most metabolic changes during submaximal aerobic exercise are closely tethered to absolute ATP turnover rate (workload), regardless of fitness or metabolic health status.

Gut microbiota diversity is associated with cardiorespiratory fitness in post-primary treatment breast cancer survivors.

NEW FINDINGS: What is the central question of this study? Does the link between cardiorespiratory fitness and gut microbiota diversity persist after adjusting for the potential effects of percentage body fat and activity-related energy expenditure (AEE)? What is the main finding and its importance? This is the first study to examine the link between cardiorespiratory fitness and gut microbiota diversity while accounting for the underlying effects of percentage body fat and free-living AEE. Results from the present work suggest that cardiorespiratory fitness, not physical activity, is a superior correlate of gut microbiota diversity among post-primary treatment, non-metastatic breast cancer survivors. ABSTRACT: Cancer treatment uniquely triggers multiple physiological shifts detrimental to overall health. Although previous research indicates a link between the gut microbiota and cardiorespiratory fitness, it is unclear whether these findings are attributable to potential underlying effects of percentage body fat or free-living activity energy expenditure (AEE). The microbe composition of faecal specimens from 37 breast cancer survivors was determined using 16S microbiome analyses. Individual-sample microbiota diversity (α-diversity) and between-sample community differences (ß-diversity) were examined. Peak oxygen uptake ( V̇O2peak ) was estimated from a graded exercise test consistent with the modified Naughton protocol, in which exercise terminates at 85% of age-predicted maximal heart rate. The AEE was measured over 10 days using doubly labelled water, wherein the percentage body fat was calculated from total body water. Pearson correlations revealed α-diversity indices (Chao1, observed species, PD whole tree and Shannon) to be positively associated with V̇O2peak (r = 0.34-0.51; P < 0.05), whereas the percentage of maximal heart rate during stages 1-4 of the graded exercise test (r = -0.34 to -0.50; P < 0.05) and percentage body fat (r = -0.32 to -0.41; P < 0.05) were negatively associated with the same α-diversity indices. Multiple linear regression models showed that V̇O2peak accounted for 22 and 26% of the variance in taxonomic richness (observed species) and phylogenic diversity after adjustment for percentage body fat and menopausal status. Unweighted UniFrac (ß-diversity) was significant for several outcomes involving cardiorespiratory fitness, and significant taxa comparisons were found. Associations between gut microbiota and free-living AEE were not found. Results from the present work suggest that cardiorespiratory fitness, not physical activity, is a superior correlate of gut microbiota diversity.

Differences in Glucose Metabolism Among Women With Spinal Cord Injury May Not Be Fully Explained by Variations in Body Composition.

OBJECTIVE: To investigate the differences in glucose metabolism among women with paraplegic, and tetraplegic spinal cord injury (SCI) in comparison to their able-bodied (AB) counterparts after adjusting for differences in body composition. DESIGN: Cross-sectional study. After an overnight fast, each participant consumed a 75-g glucose solution for oral glucose tolerance test (OGTT). Blood glucose, insulin, and C-peptide concentrations were analyzed before and 30, 60, 90, and 120 minutes after ingesting glucose solution. Insulin sensitivity index (ISI) was estimated using the Matsuda index. Percentage fat mass (%FM) and total body lean mass (TBLM) were estimated using data from dual-energy x-ray absorptiometry. Visceral fat (VF) was quantified using computed tomography. Outcome measures were compared among groups using analysis of covariance with %FM (or VF) and TBLM as covariates. SETTING: Research university. PARTICIPANTS: Women (N=42) with SCI (tetraplegia: n=8; paraplegia: n=14) and their race-, body mass index-, and age-matched AB counterparts (n=20). INTERVENTIONS: Not applicable. RESULTS: At fasting, there was no difference in glucose homeostasis (glucose, insulin, C-peptide concentrations) among 3 groups of women. In contrast, glucose, insulin, and C-peptide concentrations at minute 120 during OGTT were higher in women with tetraplegia versus women with paraplegia and AB women (P<.05, adjusted for TBLM and %FM). In addition, women with tetraplegia had lower ISI (P<.05, adjusted for TBLM and %FM) versus AB women. These differences remained after adjusting for VF and TBLM. CONCLUSION: Our study confirms that impaired glucose metabolism among women with tetraplegia may not be fully explained by changes in their body composition. Future studies exploring additional factors involved in glucose metabolism are warranted.

Inverse association between changes in energetic cost of walking and vertical accelerations in non-metastatic breast cancer survivors.

PURPOSE: With accelerometry, the utility to detect changes in physical activity are predicated on the assumption that walking energetics and gait mechanics do not change. The present work examined associations between changes (∆) in walking energetics, exercise self-efficacy, and several accelerometer-derived metrics. METHODS: Secondary analyses were performed among a sub-sample (n = 29) of breast cancer survivors participating in a larger randomized trial. During 4 min of treadmill walking (0.89 m s-1, 0% grade), indirect calorimetry quantified steady-state energy expenditure (EE), wherein, participants were fitted with a heart rate monitor and hip-worn triaxial accelerometer. Exercise self-efficacy was measured using a 9-item questionnaire, while vector magnitude (VM) and individual planes (e.g., mediolateral, vertical, and anteroposterior) of the movement were extracted for data analyses. Evaluations were made at baseline and after 3 months. RESULTS: From baseline to 3 months, the energetic cost of walking (kcals min-1) significantly decreased by an average of - 5.1% (p = 0.001; d = 0.46). Conversely, VM significantly increased (p = 0.007; d = 0.53), exclusively due to greater vertical accelerations (acc) (+ 5.7 ± 7.8 acc; p = 0.001; d = 0.69). Changes in vertical accelerations were inversely and positively associated with ∆walking EE (r = - 0.37; p = 0.047) and ∆exercise self-efficacy (r = 0.39; p = 0.034), respectively. CONCLUSION: Hip-worn accelerometers do not appear well-suited to correctly detect changes in ease of walking as evidenced by reduced energetic cost. Further research should determine if a divergence between measured EE and vertical accelerations could contribute to erroneous inferences in free-living physical activity.

Ease of walking associates with greater free-living physical activity and reduced depressive symptomology in breast cancer survivors: pilot randomized trial.

PURPOSE: We hypothesized exercise training-induced improvements in ease of walking would associate with favorable changes in objectively measured physical activity (PA) and self-reported depressive symptoms following a PA behavior-change intervention in non-metastatic breast cancer survivors (BCS). METHODS: Twenty-seven BCS received random assignment to an intervention (INT) or control group (CON). INT included counseling/group discussions coupled with supervised exercise tapered to unsupervised exercise. PA, depressive symptoms, and ease of walking were evaluated pre-/post-intervention using 10-day accelerometry, HADS depression subscale, and indirect calorimetry during a standardized treadmill test, respectively. PA composite score was calculated by converting weekly minutes of moderate-to-vigorous PA and average steps/day to z-scores then dividing the sum by 2. Cardiac efficiency was determined by dividing steady-state oxygen uptake by heart rate to evaluate the volume of oxygen consumed per heartbeat. RESULTS: ANCOVA revealed a significant time by group interaction showing the INT group exhibited greater positive changes in the PA composite compared to the CON (INT, + 0.14 ± 0.66 au vs. CON, - 0.48 ± 0.49 au; p = 0.019; η p2 = 0.21). Changes occurring from baseline to follow-up, among all participants, revealed improved ease of walking (less oxygen uptake) associated with increased PA composite (r = - 0.52; p = 0.010) and lower depressive symptomology (r = 0.50; p = 0.012) adjusted for age, race, and months since cancer diagnosis. Increased cardiac efficiency during the standardized treadmill test also associated with less daily sedentary time (r = - 0.52; p = 0.021). CONCLUSIONS: These data support the assertion that reducing the physiological difficulty of walking may contribute to greater engagement in free-living PA, less sedentary time, and decreased psychosocial distress among BCS.

Inverse relationship between changes of maximal aerobic capacity and changes in walking economy after weight loss.

PURPOSE: The aims of this study were to: (1) determine the relationships between maximum oxygen uptake ([Formula: see text]O2max) and walking economy during non-graded and graded walking among overweight women and (2) examine potential differences in [Formula: see text]O2max and walking economy before and after weight loss. METHODS: One-hundred and twenty-four premenopausal women with a body mass index (BMI) between 27 and 30 kg/m2 were randomly assigned to one of three groups: (a) diet only; (b) diet and aerobic exercise training; and (c) diet and resistance exercise training. All were furnished with standard, very-low calorie diet to reduce BMI to < 25 kg/m2. [Formula: see text]O2max was measured using a modified-Bruce protocol while walking economy (1-net [Formula: see text]O2) was obtained during fixed-speed (4.8 k·h-1), steady-state treadmill walking at 0% grade and 2.5% grade. Assessments were conducted before and after achieving target BMI. RESULTS: Prior to weight loss, [Formula: see text]O2max was inversely related (P < 0.05) with non-graded and graded walking economy (r = - 0.28 to - 0.35). Similar results were also observed following weight loss (r = - 0.22 to - 0.28). Additionally, we also detected a significant inverse relationship (P < 0.05) between the changes (∆, after weight loss) in ∆[Formula: see text]O2max, adjusted for fat-free mass, with non-graded and graded ∆walking economy (r = - 0.37 to - 0.41). CONCLUSIONS: Our results demonstrate [Formula: see text]O2max and walking economy are inversely related (cross-sectional) before and after weight loss. Importantly though, ∆[Formula: see text]O2max and ∆walking economy were also found to be inversely related, suggesting a strong synchrony between maximal aerobic capacity and metabolic cost of exercise.

Divergent Blood Pressure Response After High-Intensity Interval Exercise: A Signal of Delayed Recovery?

Hunter, GR, Fisher, G, Bryan, DR, Borges, JH, and Carter, SJ. Divergent blood pressure response after high-intensity interval exercise: a signal of delayed recovery? J Strength Cond Res 32(11): 3004-3010, 2018-The objective of this commentary is to highlight potential factors influential to the adaptation of high-intensity exercise. Herein, we present a rationale supporting the contention that elevated systolic blood pressure, after a bout of high-intensity exercise, may be indicative of delayed/incomplete recovery. Relative to type I skeletal muscle fibers, the unique cellular/vascular characteristics of type II muscle fibers may necessitate longer recovery periods, especially when exposed to repeated high-intensity efforts (i.e., intervals). In addition to the noted race disparities in cardiometabolic disease risk, including higher mean blood pressures, African Americans may have a larger percentage of type II muscle fibers, thus possibly contributing to noted differences in recovery after high-intensity exercise. Given that optimal recovery is needed to maximize physiological adaptation, high-intensity training programs should be individually-tailored and consistent with recovery profile(s). In most instances, even among those susceptible, the risk to nonfunctional overreaching can be largely mitigated if sufficient recovery is integrated into training paradigms.

High-intensity interval training and calorie restriction promote remodeling of glucose and lipid metabolism in diet-induced obesity.

Calorie restriction (CR) decreases adiposity, but the magnitude and defense of weight loss is less than predicted due to reductions in total daily energy expenditure (TEE). The purpose of the current investigation was to determine whether high-intensity interval training (HIIT) would increase markers of sympathetic activation in white adipose tissue (WAT) and rescue CR-mediated reductions in EE to a greater extent than moderate-intensity aerobic exercise training (MIT). Thirty-two 5-wk-old male C57BL/6J mice were placed on ad libitum HFD for 11 wk, followed by randomization to one of four groups (n = 8/group) for an additional 15 wk: 1) CON (remain on HFD), 2) CR (25% lower energy intake), 3) CR + HIIT (25% energy deficit created by 12.5% CR and 12.5% EE through HIIT), and 4) CR + MIT (25% energy deficit created by 12.5% CR and 12.5% EE through MIT). Markers of adipose thermogenesis (Ucp1, Prdm16, Dio2, and Fgf21) were unchanged in either exercise group in inguinal or epididymal WAT, whereas CR + HIIT decreased Ucp1 expression in retroperitoneal WAT and brown adipose tissue. HIIT rescued CR-mediated reductions in lean body mass (LBM) and resting energy expenditure (REE), and both were associated with improvements in glucose/insulin tolerance. Improvements in glucose metabolism in the CR + HIIT group appear to be linked to a molecular signature that enhances glucose and lipid storage in skeletal muscle. Exercise performed at either moderate or high intensity does not increase markers of adipose thermogenesis when performed in the presence of CR but remodels skeletal muscle metabolic and thermogenic capacity.

Presurgical weight loss affects tumour traits and circulating biomarkers in men with prostate cancer.

BACKGROUND: Obesity is associated with aggressive prostate cancer. To explore whether weight loss favourably affects tumour biology and other outcomes, we undertook a presurgical trial among overweight and obese men with prostate cancer. METHODS: This single-blinded, two-arm randomised controlled trial explored outcomes of a presurgical weight loss intervention (WLI) that promoted ∼1 kg per week loss via caloric restriction and increased physical activity (PA). Forty overweight/obese men with clinically confirmed prostate cancer were randomised to the WLI presurgery or to a control arm; changes in weight, body composition, quality-of-life, circulating biomarkers, gene expression, and immunohistochemical markers in tumour and benign prostatic tissue were evaluated. RESULTS: The study period averaged 50 days. Mean (s.d.) change scores for the WLI vs control arms were as follows: weight: -4.7 (3.1) kg vs -2.2 (4.4) kg (P=0.0508); caloric intake: -500 (636) vs -159 (600) kcal per day (P=0.0034); PA: +0.9 (3.1) vs +1.7 (4.6) MET-hours per day (NS); vitality: +5.3 (7.l4) vs -1.8 (8.1) (P=0.0491); testosterone: +55.1 (86.0) vs -48.3 (203.7) ng dl-1 (P=0.0418); sex hormone-binding globulin: +14.0 (14.6) vs +1.8 (7.6) nmol l-1 (P=0.0023); and leptin: -2.16 (2.6) vs -0.03 (3.75) (P=0.0355). Follow-up Ki67 was significantly higher in WLI vs control arms; median (interquartile range): 5.0 (2.5,10.0) vs 0.0 (0.0,2.5) (P=0.0061) and several genes were upregulated, for example, CTSL, GSK3B, MED12, and LAMC2. CONCLUSIONS: Intentional weight loss shows mixed effects on circulating biomarkers, tumour gene expression, and proliferative markers. More study is needed before recommending weight loss, in particular rapid weight loss, among men with prostate cancer.

Acylcarnitines as markers of exercise-associated fuel partitioning, xenometabolism, and potential signals to muscle afferent neurons.

NEW FINDINGS: What is the central question of this study? Does improved metabolic health and insulin sensitivity following a weight-loss and fitness intervention in sedentary, obese women alter exercise-associated fuel metabolism and incomplete mitochondrial fatty acid oxidation (FAO), as tracked by blood acylcarnitine patterns? What is the main finding and its importance? Despite improved fitness and blood sugar control, indices of incomplete mitochondrial FAO increased in a similar manner in response to a fixed load acute exercise bout; this indicates that intramitochondrial muscle FAO is inherently inefficient and is tethered directly to ATP turnover. With insulin resistance or type 2 diabetes mellitus, mismatches between mitochondrial fatty acid fuel delivery and oxidative phosphorylation/tricarboxylic acid cycle activity may contribute to inordinate accumulation of short- or medium-chain acylcarnitine fatty acid derivatives [markers of incomplete long-chain fatty acid oxidation (FAO)]. We reasoned that incomplete FAO in muscle would be ameliorated concurrent with improved insulin sensitivity and fitness following a ∼14 week training and weight-loss intervention in obese, sedentary, insulin-resistant women. Contrary to this hypothesis, overnight-fasted and exercise-induced plasma C4-C14 acylcarnitines did not differ between pre- and postintervention phases. These metabolites all increased robustly with exercise (∼45% of pre-intervention peak oxygen consumption) and decreased during a 20 min cool-down. This supports the idea that, regardless of insulin sensitivity and fitness, intramitochondrial muscle ß-oxidation and attendant incomplete FAO are closely tethered to absolute ATP turnover rate. Acute exercise also led to branched-chain amino acid acylcarnitine derivative patterns suggestive of rapid and transient diminution of branched-chain amino acid flux through the mitochondrial branched-chain ketoacid dehydrogenase complex. We confirmed our prior novel observation that a weight-loss/fitness intervention alters plasma xenometabolites [i.e. cis-3,4-methylene-heptanoylcarnitine and γ-butyrobetaine (a co-metabolite possibly derived in part from gut bacteria)], suggesting that host metabolic health regulated gut microbe metabolism. Finally, we considered whether acylcarnitine metabolites signal to muscle-innervating afferents; palmitoylcarnitine at concentrations as low as 1-10 µm activated a subset (∼2.5-5%) of these neurons ex vivo. This supports the hypothesis that in addition to tracking exercise-associated shifts in fuel metabolism, muscle acylcarnitines act as signals of exertion to short-loop somatosensory-motor circuits or to the brain.

Associations of human skeletal muscle fiber type and insulin sensitivity, blood lipids, and vascular hemodynamics in a cohort of premenopausal women.

PURPOSE: Cardiometabolic disease remains a leading cause of morbidity and mortality in developed nations. Consequently, identifying and understanding factors associated with underlying pathophysiological processes leading to chronic cardio metabolic conditions is critical. Metabolic health, arterial elasticity, and insulin sensitivity (SI) may impact disease risk, and may be determined in part by myofiber type. Therefore, the purpose of this study was to test the hypothesis that type I myofiber composition would be associated with high SI, greater arterial elasticity, lower blood pressure, and blood lipids; whereas, type IIx myofibers would be associated with lower SI, lower arterial elasticity, higher blood pressure, blood lipids. METHODS: Muscle biopsies were performed on the vastus lateralis in 16 subjects (BMI = 27.62 ± 4.71 kg/m2, age = 32.24 ± 6.37 years, 43% African American). The distribution of type I, IIa, and IIx myofibers was determined via immunohistochemistry performed on frozen cross-sections. Pearson correlation analyses were performed to assess associations between myofiber composition, SI, arterial elasticity, blood pressure, and blood lipid concentrations. RESULTS: The percentage of type I myofibers positively correlated with SI and negatively correlated with systolic blood pressure SBP, diastolic blood pressure, and mean arterial pressure (MAP); whereas, the percentage of type IIx myofibers were negatively correlated with SI and large artery elasticity, and positively correlated with LDL cholesterol, SBP, and MAP. CONCLUSIONS: These data demonstrate a potential link between myofiber composition and cardiometabolic health outcomes in a cohort of premenopausal women. Future research is needed to determine the precise mechanisms in which myofiber composition impacts the pathophysiology of impaired glucose and lipid metabolism, as well as vascular dysfunction.

Alterations in Hemoglobin and Serum 25-hydroxyvitamin D are Related Before and After Weight Loss Independent of African Admixture.

African American (AA) and European American (EA) women often exhibit differences in hemoglobin (Hb) and 25-hydroxyvitamin D [25(OH)D], both of which can be altered by calorie restriction leading to weight loss. Given these known differences, it is of clinical interest to examine the potential for race-specific, adverse responses to weight loss. Sixty-four overweight (BMI 27-29.9 kg/m2), premenopausal women consumed a standardized, very-low calorie diet to reduce BMI < 25 kg/m2. Ancestry informative markers provided estimates of African admixture, an objective mean of expressing race. Blood sampling and anthropometric measures were performed at baseline and upon meeting target BMI. At baseline, in the overweight state, Hb (g/dL) (AA, 11.7 ± 0.9 vs. EA, 12.5 ± 0.8; p < .01) and 25(OH)D (nmol/L) (AA, 35.7 ± 12.9 vs. EA, 57.0 ± 20.0; p < .01) were lower in AAs. After weight loss, Hb decreased (AA, -0.5 ± 0.7 vs. EA, -0.4 ± 0.6; p = .48) to a similar extent among races. Conversely, 25(OH)D increased (AA, 43.4 ± 14.0 vs. EA 68.2 ± 24.3; p < .01) though the magnitude of change (Δ) was not different (AA, +7.8 ± 13.5 vs. EA, +11.2 ± 16.7; p = .37) between races. Multiple linear regression revealed a positive association between ΔHb and Δ25(OH)D (r = .386; p < .01) adjusted for African admixture, Δtestosterone, and Δbody fat%. Path analyses revealed a significant indirect effect of Δbody fat% on ΔHb through Δ25(OH)D, ß =-0.023, CI [-0.06, -0.004]. Following 15% weight loss, participants with the largest increase in serum 25(OH)D exhibited the smallest decrease in Hb. Future research should clarify the optimal degree of calorie restriction to stimulate weight loss while mitigating the potential risk of anemia associated with dieting efforts.