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The purpose of this experiment was to learn whether low doses of caffeine have ergogenic, perceptual, and metabolic effects during cycling. To determine the effects of 1, 2, and 3 mg/kg caffeine on cycling performance, differentiated ratings of perceived exertion (D-RPE), quadriceps pain intensity, and metabolic responses to cycling exercise, 13 cyclists exercised on a stationary ergometer for 15 min at 80% VO2peak, then, after 4 min of active recovery, completed a 15-min performance ride 60 min after ingesting caffeine or placebo. Work done (kJ/kg) during the performance ride was used as a measure of performance. D-RPE, pain ratings, and expired-gas data were obtained every 3 min, and blood lactate concentrations were obtained at 15 and 30 min. Compared with placebo, caffeine doses of 2 and 3 mg/kg increased performance by 4% (95% CI: 1.0-6.8%, p = .02) and 3% (95% CI: -0.4% to 6.8%, p = .077), respectively. These effects were ergogenic, on average, but varied considerably in magnitude among individual cyclists. There were no effects of caffeine on D-RPE or pain throughout the cycling task. Selected metabolic variables were affected by caffeine, consistent with its known actions. The authors conclude that caffeine preparations of 2 and 3 mg/kg enhanced performance, but future work should aim to explain the considerable interindividual variability of the drug's ergogenic properties. [ABSTRACT FROM AUTHOR]

The influence of menstrual cycle phase and fitness status on metabolism during high-intensity interval exercise (HIIE) was assessed. Twenty-five females (24.4 (3.6) years) were categorized by normal menstrual cycle (n = 14) vs. oral contraceptive (OC) use (n = 11) and by aerobic fitness, high-fitness females (HFF; n = 13) vs. low-fitness females (LFF; n = 12). HIIE was four sets of four repetitions with a 3 min rest between intervals on a cycle ergometer at a power output halfway between the ventilatory threshold and V̇O2peak and performed during follicular (FOL: days 2–7 or inactive pills) and luteal phases (LUT: day ∼21 or 3rd week of active pills). Substrate oxidation was assessed via indirect calorimetry, blood lactate via finger stick, and recovery of skeletal muscle oxidative metabolism (mV̇O2) via continuous-wave near-infrared spectroscopy. HFF oxidized more fat (g·kg−1) during the full session (FOL: p = 0.050, LUT: p = 0.001), high intervals (FOL: p = 0.048, LUT: p = 0.001), low intervals (FOL: p = 0.032, LUT: p = 0.024), and LUT recovery (p = 0.033). Carbohydrate oxidation area under the curve was greater in HFF during FOL (FOL: p = 0.049, LUT: p = 0.124). Blood lactate was lower in LFF in FOL (p ≤ 0.05) but not in LUT. Metabolic flexibility (Δ fat oxidation g·kg−1·min−1) was greater in HFF than LFF during intervals 2–3 in FOL and 1–4 in LUT (p ≤ 0.05). Fitness status more positively influences exercise metabolic flexibility during HIIE than cycle phase or OC use. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to compare ultrasound echo intensity (EI) with high-resolution T1 -weighted MRI and to establish calibration equations to estimate percent intramuscular fat from EI.Methods: Thirty-one participants underwent both ultrasound and MRI testing of 4 muscles: rectus femoris (RF); biceps femoris (BF); tibialis anterior (TA); and medial gastrocnemius (MG).Results: Strong correlations were found between MRI percent fat and muscle EI after correcting for subcutaneous fat thickness (r = 0.91 in RF, r = 0.80 in BF, r = 0.80 in TA, r = 0.76 in MG). Three types of calibration equations were established.Conclusions: Muscle ultrasound is a practical and reproducible method that can be used as an imaging technique for examination of percent intramuscular fat. Future ultrasound studies are needed to establish equations for other muscle groups to enhance its use in both research and clinical settings. [ABSTRACT FROM AUTHOR]

Pecans are rich in bioactive compounds known to reduce oxidative stress and provide glucoregulatory benefits. Few studies assessing the effect of a pecan-enriched diet on such health outcomes suggest potential improvements to cardiometabolic health; however, this has not been studied in an older adult population. Thus, we aimed to examine the effect of daily pecan consumption for 4-weeks on fasting and postmeal antioxidant status, oxidative stress, and markers of glycemia in healthy aging adults. In this randomized, parallel, controlled trial, 41 healthy adults (50–75 years) either consumed 68 g of pecans/day (pecan; n = 21) or avoided all nuts (control; n = 20). At pre- (V1) and postintervention visits (V2), blood samples were obtained at fasting, and 30, 60, and 120 min following a high saturated fat meal to assess changes in malondialdehyde, which is a measure of lipid peroxidation, total antioxidant capacity (TAC), glucose, and insulin. Across the intervention, there were no differences in fasting or postprandial TAC, glucose, or insulin for pecan versus control. There was a trend for a difference in fasting lipid peroxidation from V1 to V2 by treatment (P = .06) driven by a slight reduction for pecan versus control (Δpecan: −2.0 ± 1.1 vs. Δcontrol: +0.6 ± 0.8 μM). In addition, postprandial lipid peroxidation was suppressed at V2 for pecan, and this was different from control (pecan areas under the curve (AUC): 10.6 ± 1.3 μM/h to 9.1 ± 1.2 μM/h vs. control AUC: 8.9 ± 1.3 μM/h to 9.2 ± 1.1 μM/h; P = .03). These findings suggest that a 1 month, pecan-enriched diet is protective against postmeal oxidative stress. Longer interventions or a diabetic population may be needed to observe glucoregulatory benefits. Clinical Trial Registration: NCT04385537. [ABSTRACT FROM AUTHOR]

We used next-generation RNA sequencing (RNA-Seq) technology on the whole transcriptome to identify genes whose expression is consistently affected by obesity across multiple arteries. Specifically, we examined transcriptional profiles of the iliac artery as well as the feed artery, first, second, and third branch order arterioles in the soleus, gastrocnemius, and diaphragm muscles from obese Otsuka Long-Evans Tokushima Fatty (OLETF) and lean Long-Evans Tokushima Otsuka (LETO) rats. Within the gastrocnemius and soleus muscles, the number of genes differentially expressed with obesity tended to increase with increasing branch order arteriole number (i.e., decreasing size of the artery). This trend was opposite in the diaphragm. We found a total of 15 genes that were consistently upregulated with obesity (MIS18A, CTRB1, FAM151B, FOLR2, PXMP4, OAS1B, SREBF2, KLRA17, SLC25A44, SNX10, SLFN3, MEF2BNB, IRF7, RAD23A, LGALS3BP) and five genes that were consistently downregulated with obesity (C2, GOLGA7, RIN3, PCP4, CYP2E1). A small fraction (9%) of the genes affected by obesity was modulated across all arteries examined. In conclusion, the present study identifies a select number of genes (i.e., 20 genes) whose expression is consistently altered throughout the arterial network in response to obesity and provides further insight into the heterogeneous vascular effects of obesity. Although there is no known direct function of the majority of 20 genes related to vascular health, the obesity-associated upregulation of SREBF2, LGALS3BP, IRF7, and FOLR2 across all arteries is suggestive of an unfavorable vascular phenotypic alteration with obesity. These data may serve as an important resource for identifying novel therapeutic targets against obesity-related vascular complications. [ABSTRACT FROM AUTHOR]

Adipose tissue (AT)-derived cytokines are proposed to contribute to obesity-associated vascular insulin resistance. We tested the hypothesis that voluntary physical activity and diet restriction-induced maintenance of body weight would both result in decreased AT inflammation and concomitant improvements in insulin-stimulated vascular relaxation in the hyperphagic, obese Otsuka Long-Evans Tokushima fatty (OLETF) rat. Rats (aged 12 wk) were randomly assigned to sedentary (SED; n = 10), wheel running (WR; n = 10), or diet restriction (DR; n = 10; fed 70% of SED) for 8 wk. WR and DR rats exhibited markedly lower adiposity (7.1 = 0.4 and 15.7 = 1.1% body fat, respectively) relative to SED (27 = 1.2% body fat), as well as improved blood lipid profiles and systemic markers of insulin resistance. Reduced adiposity in both WR and DR was associated with decreased AT mRNA expression of inflammatory genes (e.g., MCP-1, TNF-ɑ, and IL-6) and markers of immune cell infiltration (e.g., CD8, CD11c, and F4/80). The extent of these effects were most pronounced in visceral AT compared with subcutaneous and periaortic AT. Markers of inflammation in brown AT were upregulated with WR but not DR. In periaortic AT, WR- and DR-induced reductions in expression and secretion of cytokines were accompanied with a more atheroprotective gene expression profile in the adjacent aortic wall. WR, but not DR, resulted in greater insulin-stimulated relaxation in the aorta; an effect that was, in part, mediated by a decrease in insulin-induced endothelin-1 activation in WR aorta. Collectively, we show in OLETF rats that lower adiposity leads to less AT and aortic inflammation, as well as an exercise-specific improvement in insulin-stimulated vasorelaxation. [ABSTRACT FROM AUTHOR]

New findings What is the central question of this study? This study investigated the influence of obesity on insulin-induced vasomotor reactivity in rat skeletal muscle feed arteries., What is the main finding and its importance? Irrespective of obesity, the gastrocnemius feed artery displayed diminished insulin-induced vasodilatory response compared to the soleus feed artery. This difference between the arteries was abolished in the presence of an endothelin-1 receptor antagonist. Therefore, our findings demonstrate that insulin-induced endothelin-1 production is not uniform among all skeletal muscle resistance vessels., The vascular actions of insulin are complex, because it can stimulate both nitric oxide-mediated dilatation and endothelin (ET)-1-mediated constriction. We examined vasoreactivity to insulin in isolated feed arteries of the gastrocnemius (GFA) and soleus muscles (SFA) of 32-week-old Long-Evans Tokushima Otsuka (LETO) and Otsuka Long-Evans Tokushima fatty (OLETF) rats, a hyperphagic rodent model of obesity and insulin resistance. The insulin-induced vasoreactivity of SFA and GFA was similar in LETO (healthy) and OLETF (obese/insulin-resistant) rats. However, examination of between-vessel effects revealed a number of novel insights into the heterogeneous vascular effects of insulin. Soleus feed arteries dilated more than GFA in LETO at 100 and 1000 μIU ml−1 insulin (23 versus 6 and 28 versus 0%, respectively; P < 0.05 for between-vessel differences). Likewise, in OLETF rats there was significantly greater dilatation in SFA than GFA at 10, 100 and 1000 μIU ml−1 insulin (28 versus 3, 30 versus 0 and 34 versus 0%, respectively; all P < 0.05). In the presence of 3 μ m tezosentan, a non-specific endothelin-1 receptor blocker, insulin-induced dilatation of the GFA was enhanced such that differences between vessels were largely abolished in both groups. Furthermore, acetylecholine-induced dilatation was significantly greater in SFA than GFA within each group, whereas sodium nitroprusside-induced dilatory responses were greater in the GFA compared with the SFA. Overall, our findings indicate that the insulin/endothelin-1 vasoconstrictor pathway is more active in GFA than in SFA, independent of obesity in the OLETF rat model. [ABSTRACT FROM AUTHOR]

Many diseases associated with sympathoexcitation also exhibit elevated reactive oxygen species (ROS). A recent animal study indicated that exogenous administration of the sympathetic neurotransmitter norepinephrine (NE) increased systemic ROS via circulating leukocytes. The mechanisms contributing to this effect of NE and whether these findings can be translated to humans is unknown. Thus we tested the hypothesis that NE increases superoxide production in human peripheral blood mononuclear cells (PBMCs) via NADPH oxidase. Primary human PBMCs were freshly isolated from healthy young men and placed in culture. After NE (50 pg/ml, 50 ng/ml, and 50 μg/ml concentrations) or control treatments, NADPH oxidase mRNA expression (gp91phox, p22phox, and p67phox) was assessed using real-time RT-PCR, and intracellular superoxide production was measured using dihydroethidium fluorescence. PBMCs were also treated with selective adrenergic agonists-antagonists to determine the receptor population involved. In addition, CD14+ monocyte-endothelial cell adhesion was determined using a fluorescent-based assay. NE significantly increased NADPH oxidase gene expression and intracellular superoxide production in a time-dependent manner (superoxide: 0.9 ± 0.2 fold, 6 h vs. 3.0 ± 0.3 fold, 36 h; NE, 50 μg/ml; P < 0.05). The sustained increase in NE-induced superoxide production was primarily mediated via a-adrenergic receptors, preferentially a2-receptors. The NADPH oxidase blocker diphenylene iodonium and protein kinase C inhibitor Staurosporine significantly attenuated NE-induced increases in superoxide production. Importantly, NE treatment increased CD14+ monocyte-endothelial cell adhesion. These findings indicate for the first time that NE increases superoxide production in freshly isolated primary human PBMCs via NADPH oxidase through a-adrenergic receptors, an effect facilitating monocyte adhesion to the endothelium. [ABSTRACT FROM AUTHOR]

New findings What is the central question of this study? What are the effects of caloric restriction and chronic exercise on β-adrenergic and natriuretic peptide receptor genes in visceral adipose tissue of obese rats?, What is the main finding and its importance? Physical activity induced increases in natriuretic peptide receptor (NPR) and β-adrenergic receptor (βAR) mRNA levels in retroperitoneal fat of obese rats. Both chronic exercise and caloric restriction enhance protein expression of βAR2 and βAR3 in the retroperitoneal adipose tissue of the Otsuka Long-Evans Tokushima Fatty rat, albeit through apparently different mechanisms. Organ culture experiments support the hypothesis that increases in nitric oxide interact synergistically with adrenaline and atrial natriuretic peptide signalling in control of the expression of βAR2 and NPR2 mRNAs., The mechanisms underlying exercise-induced increases in adipose tissue blood flow and lipolysis involve both β-adrenergic receptor (βAR)- and natriuretic peptide receptor (NPR)-dependent processes. We hypothesized that daily wheel running (RUN) would increase the expression of NPR1, NPR2, βAR2 and βAR3 in retroperitoneal (RP) and epididymal (EPI) adipose tissues of obese Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Four-week-old OLETF rats were assigned to sedentary (SED, n= 6), calorie-restricted (CR, n= 8; fed 70% of SED) or RUN groups ( n= 8). Rats were killed at 40 weeks of age. By design, body weight and adiposity were similar between RUN and CR animals, but each was lower than SED ( P < 0.01). Compared with SED, RP depots of RUN rats exhibited 1.7- to 3.2-fold greater NPR1, NPR2, βAR2 and βAR3 mRNA levels (all P < 0.05). There were no differences between CR and SED in the expression of these genes in RP adipose tissues, and there were no differences in gene expression among groups in EPI adipose tissues. At the protein level, βAR2 and βAR3 were elevated in RUN and CR groups relative to the SED group in RP adipose tissues. In order to gain insight into the mechanisms underlying the activity-induced increases in NPR and βAR mRNAs, RP adipose tissue explants from Wistar rats were treated with atrial natriuretic peptide (ANP), adrenaline and/or S-nitroso- N-acetyl- dl-penicillamine (SNAP; a nitric oxide donor) in organ culture experiments. SNAP synergistically enhanced adrenaline- and ANP-stimulated increases in NPR2 and βAR2 mRNA levels. Our data suggest that physical activity-induced increases in nitric oxide interact with adrenaline and ANP to trigger the induction of NPR and βAR mRNAs in the RP adipose tissue depot of the OLETF rat. [ABSTRACT FROM AUTHOR]

We adopted a transcriptome-wide microarray analysis approach to determine the extent to which vascular gene expression is altered as a result of juvenile obesity and identify obesity-responsive mRNAs. We examined transcriptional profiles in the left anterior descending coronary artery (LAD), perivascular fat adjacent to the LAD, and descending thoracic aorta between obese (n= 5) and lean (n= 6) juvenile Ossabaw pigs (age = 22 wk). Obesity was experimentally induced by feeding the animals a high-fat/high-fructose corn syrup/high-cholesterol diet for 16 wk. We found that expression of 189 vascular cell genes in the LAD and expression of 165 genes in the thoracic aorta were altered with juvenile obesity (false discovery rate ≤ 10%) with an overlap of only 28 genes between both arteries. Notably, a number of genes found to be markedly upregulated in the LAD of obese pigs are implicated in atherosclerosis, including ACP5, LYZ, CXCL14, APOE, PLA2G7, LGALS3, SPP1, ITGB2, CYBB, and P2RY12. Furthermore, pathway analysis revealed the induction of proinflammatory and pro-oxidant pathways with obesity primarily in the LAD. Gene expression in the LAD perivascular fat was minimally altered with juvenile obesity. Together, we provide new evidence that obesity produces artery-specific changes in pretranslational regulation with a clear upregulation of proatherogenic genes in the LAD. Our data may offer potential viable drug targets and mechanistic insights regarding the molecular precursors involved in the origins of overnutrition and obesity-associated vascular disease. In particular, our results suggest that the oxidized LDL/LOX-1/NF-κB signaling axis may be involved in the early initiation of a juvenile obesity-induced proatherogenic coronary artery phenotype. [ABSTRACT FROM AUTHOR]

Perivascular adipose tissue (PVAT) is implicated as a source of proatherogenic cytokines. Phenotypic differences in local PVAT depots may contribute to differences in disease susceptibility among arteries and even regions within an artery. It has been proposed that PVAT around the abdominal and thoracic aorta shares characteristics of white and brown adipose tissue (BAT), respectively; however, a detailed comparison of the phenotype of these PVAT depots has not been performed. Using young and older adult rats, we compared the phenotype of PVATs surrounding the abdominal and thoracic aorta to each other and also to epididymal white and subscapular BAT. Compared with young rats, older rats exhibited greater percent body fat (34.5 ± 3.1 vs. 10.4 ± 0.9%), total cholesterol (112.2 ± 7.5 vs. 58.7 ± 6.3 mg/dl), HOMA-insulin resistance (1.7 ± 0.1 vs. 0.9 ± 0.1 a.u.), as well as reduced ACh-induced relaxation of the aorta (maximal relaxation: 54 ± 10 vs. 77 ± 6%) (all P < 0.05). Expression of inflammatory genes and markers of immune cell infiltration were greater in abdominal PVAT than in thoracic PVAT, and overall, abdominal and thoracic PVATs resembled the phenotype of white adipose tissue (WAT) and BAT, respectively. Histology and electron microscopy indicated structural similarity between visceral WAT and abdominal PVAT and between BAT and thoracic PVAT. Our data provide evidence that abdominal PVAT is more inflamed than thoracic PVAT, a difference that was by and large independent of sedentary aging. Phenotypic differences in PVAT between regions of the aorta may be relevant in light of the evidence in large animals and humans that the abdominal aorta is more vulnerable to atherosclerosis than the thoracic aorta. [ABSTRACT FROM AUTHOR]

High-intensity functional training (HIFT) can play a major role in preventing cardiometabolic disease. The majority of HIFT interventions incorporate CrossFit (CF) training. We measured aerobic capacity, metabolic response during high-intensity interval exercise (HIIE), resting mitochondrial oxidative capacity, and resting vascular function in adults who participated in CF training (> one year) vs. a sedentary group completing <2 h·wk-1 of structure exercise for > one year (SED). Twenty-one participants were recruited (CF n = 13 vs. SED n = 8). CF participants had a 33.0% greater relative VO2 peak (p<.001) and lower body fat percentage (CF = 18.6 [3.8] vs. SED = 30.3 [8.4]; p<.001). CF participants had higher exercising substrate oxidation when expressed as absolute and body weight relative values (p<.013), but not when expressed relative to lean mass (p>.200). CF participants had greater mitochondrial oxidative capacity (p=.014). There were no differences in large artery function, but CF participants had greater baseline arterial diameter (p=.004) and faster reperfusion following arterial occlusion (p<.05). These data support HIFT programs' effectiveness in improving fitness, weight status, and metabolic, mitochondrial, and vascular function. [ABSTRACT FROM AUTHOR]

Early vascular changes at the molecular level caused by adoption of a sedentary lifestyle are incompletely characterized. Herein, we employed the rodent wheel-lock model to identify mRNAs in the arterial wall that are responsive to the acute transition from higher to lower levels of daily physical activity. Specifically, we evaluated whether short-term cessation of voluntary wheel running alters vascular mRNA levels in rat conduit arteries previously reported to have marked increases (i.e. iliac artery) versus marked decreases (i.e. renal artery) in blood flow during running. We used young female Wistar rats with free access to voluntary running wheels. Following 23 days of voluntary running (average distance of ∼15 km per night; ∼4.4 h per night), rats in one group were rapidly transitioned to a sedentary state by locking the wheels for 7 days ( n= 9; wheel-lock 7 day rats) or remained active in a second group for an additional 7 days ( n= 9; wheel-lock 0 day rats). Real-time PCR was conducted on total RNA isolated from iliac and renal arteries to evaluate expression of 25 pro-atherogenic and anti-atherogenic genes. Compared with the iliac arteries of wheel-lock 0 day rats, iliac arteries of wheel-lock 7 day rats exhibited increased expression of TNFR1 (+19%), ET1 (+59%) and LOX-1 (+31%; all P < 0.05). Moreover, compared with renal arteries of wheel-lock 0 day rats, renal arteries of wheel-lock 7 day rats exhibited decreased expression of ETb (−23%), p47phox (−32%) and p67phox (−19%; all P < 0.05). These data demonstrate that cessation of voluntary wheel running for 7 days produces modest, but differential changes in mRNA levels between the iliac and renal arteries of healthy rats. This heterogeneous influence of short-term physical inactivity could be attributed to the distinct alteration in haemodynamic forces between arteries. [ABSTRACT FROM AUTHOR]

The article focuses on a study related to the impact of aerobic training on glucose tolerance in prediabetic and normoglycemic persons. It is hypothesized in the study that prediabetic subjects would have more endurance training-induced changes in plasma glucose and insulin responses to an oral glucose challenge. Another hypothesis is that the abnormal glucose metabolism of prediabetic subjects would be completely reversed by training. It is concluded that prediabetes is linked with greater training-induced changes in glucose tolerance.

Non-Technical Summary Circulating angiogenic cells (CACs) repair and maintain the vascular endothelium. CACs are responsive to lifestyle factors such as diet and physical activity. For example, their capacity to regenerate the endothelium is impaired in cardiovascular disease patients, whereas exercise training can improve CAC function. In this study, we examined the effects of a high-fat meal with and without prior endurance exercise on several molecular aspects of CAC function, including levels of reactive oxygen species (ROS), nitric oxide (NO), intracellular lipids, and gene expression. Our results indicated that the high-fat meal induced significant oxidative stress (i.e. ROS production) in the CACs that expressed the cell surface protein CD31. However, when subjects performed a single bout of exercise on the prior day, the meal had no effect on ROS in CD31+ cells. Therefore, we concluded that prior exercise prevents the oxidative stress induced by a high-fat meal in CD31+ CACs. [ABSTRACT FROM AUTHOR]

We sought to delineate the effects of acute and chronic exercise on the regulation of intracellular nitric oxide (NOi) production in putative endothelial progenitor cells (EPCs). Putative EPC colony-forming units (CFUEC) were cultured from blood drawn before and after 30 mm of treadmill exercise at 75% of maximal oxygen uptake in active (n = 8) and inactive (n = 8) men. CFU-EC were similar between groups at baseline, but increased after exercise in active men only (P = 0.04). CFU-EC expressed lower NADPH oxidase subunit gp91phox mRNA and elevated endothelial nitric oxide synthase mRNA in active relative to inactive men at baseline (P < 0.05). Acute exercise reduced gp91phox mRNA in CFU-EC of both groups (P < 0.05), whereas p47phox mRNA levels were reduced in the inactive group only (P = 0.02). There were no differences between groups or with acute exercise in xanthine oxidase, superoxide dismutase isoforms, or gluthathione peroxidase-1 mRNA levels. NOi was significantly greater in CFU-EC of active men at baseline (P 0.004). NOi increased in CFU-EC of inactive men with acute exercise, and in vitro experiments with apocynin indicated the increased NOi production was caused by suppression of NADPH oxidase. However, the increases in NOi with the different treatments in the inactive group did not reach the baseline levels in the active group (P < 0.05). We conclude that acute exercise increases NOi in cells generated by the CFU-EC assay through an NADPH oxidase-inhibition mechanism in sedentary men. However, differences due to chronic exercise must involve additional factors. Our findings support exercise as a means to improve putative EPC function and suggest a novel mechanism that may explain this effect. [ABSTRACT FROM AUTHOR]

The purpose of this systematic review was to synthesize the results from current literature examining the effects of prior exercise on the postprandial triglyceride (TG) response to evaluate current literature and provide future direction. A quantitative review was performed using meta-analytic methods to quantify individual effect sizes. A moderator analysis was performed to investigate potential variables that could influence the effect of prior exercise on postprandial TG response. Two hundred and seventy-nine effects were retrieved from 165 studies for the total TG response and 142 effects from 87 studies for the incremental area under the curve TG response. There was a moderate effect of exercise on the total TG response (Cohen's d = −0.47; p <.0001). Moderator analysis revealed exercise energy expenditure significantly moderated the effect of prior exercise on the total TG response (p <.0001). Exercise modality (e.g., cardiovascular, resistance, combination of both cardiovascular and resistance, or standing), cardiovascular exercise type (e.g., continuous, interval, concurrent, or combined), and timing of exercise prior to meal administration significantly affected the total TG response (p <.001). Additionally, exercise had a moderate effect on the incremental area under the curve TG response (Cohen's d = −0.40; p <.0001). The current analysis reveals a more homogeneous data set than previously reported. The attenuation of postprandial TG appears largely dependent on exercise energy expenditure (∼2 MJ) and the timing of exercise. The effect of prior exercise on the postprandial TG response appears to be transient; therefore, exercise should be frequent to elicit an adaptation. [ABSTRACT FROM AUTHOR]

Background: Zinc is a micronutrient involved in the production of, and peripheral sensitivity to, pancreatic β cell-derived insulin. To our knowledge, the effect of zinc supplementation on insulin outcomes, and potential risk of diabetes, in otherwise healthy children in the United States has not been investigated.Objective: The objective of this study was to determine the influence of zinc supplementation on insulin outcomes in black and white girls in the early stages of adolescence. A secondary objective was to determine relations between baseline zinc concentrations and insulin outcomes.Methods: Healthy black and white girls aged 9-11 y were randomly assigned to daily supplementation of zinc (9 mg elemental Zn/d; n = 75; blacks: n = 35) or placebo (n = 72; blacks: n = 32) for 4 wk. Fasting serum insulin, glucose, and C-peptide were assessed at baseline and at 4 wk. C-peptide and glucose values were used to calculate the computer model-derived homeostatic model assessment of insulin resistance (HOMA2-IR). Changes in outcome measures were compared by using repeated-measures, mixed-model ANOVA.Results: Baseline plasma zinc was not correlated with C-peptide (r = -0.07), insulin (r = -0.06), or HOMA2-IR (r = -0.09) (all P > 0.05) after controlling for race and age. Treatment × time interactions for C-peptide and HOMA2-IR were not significant (both P > 0.05). Although the treatment × race × time interactions for C-peptide and HOMA2-IR were not significant (both P = 0.08), black girls who received the placebo experienced slight increases in C-peptide (15.7%) and HOMA2-IR (17.7%) (P = 0.06).Conclusions: Four weeks of zinc supplementation had no effect on insulin outcomes in healthy black and white early-adolescent girls, although C-peptide and HOMA2-IR tended to increase in black girls who received placebo. Additional trials that are appropriately powered should further explore the effect of zinc on markers of diabetes risk, and whether race affects this relation. This trial was registered at clinicaltrials.gov as NCT01892098. [ABSTRACT FROM AUTHOR]

Pecan-enriched diets have been linked to improved lipid metabolism; however, the impact of pecans on vascular health has yet to be examined. We hypothesized that 4 weeks of a pecan-enriched diet would improve fasting and postprandial blood lipids and vascular function compared with a nut-free diet. In this randomized control study, 44 older adults (59 ± 6 years) consumed 68 g of pecans/d (pecan; n = 21) or avoided all nuts (control; n = 23) for 4 weeks. At pre- and post-diet visits, fasting and postprandial blood lipids, macrovascular (by flow-mediated dilation), and microvascular (tissue saturation index reactive hyperemia [RH] kinetics by continuous-wave near-infrared spectroscopy) function were assessed. From the pre- to post-diet visit, there were greater reductions in fasting total cholesterol (pecan: –14 ± 4.0 vs control: –0.2 ± 5.4 mg/dL; P =.04), low-density lipoprotein (LDL) cholesterol (pecan: –15 ± 3.7 vs control: +1.9 ± 4.4 mg/dL; P =.01), non–high-density lipoprotein cholesterol (pecan: –15 ± 3.6 vs control: –0.5 ± 4.8 mg/dL; P =.02), LDL particle number (pecan: –126 ± 51 vs control: +43 ± 42 nmol/L; P =.01), and LDL medium (pecan: –34 ± 13 vs control: +16 ± 11 nmol/L; P <.01), for pecan vs control. Further, postprandial triglyceride was suppressed for pecan (P =.01) compared with control (P =.78). Postprandial RH slope (P =.04) and RH time to half (P =.004) was different by group, driven by improvements in pecan vs control. However, fasting macro- and microvascular function was unaffected. Daily pecan consumption for 4 weeks improved fasting and postprandial blood lipids and microvascular reactivity in older adults. Because changes in microvascular function typically precipitate macrovascular changes, long-term pecan consumption may improve vascular health and reduce risk for cardiovascular events. This trial was registered at clinicaltrials.gov (NCT04385537). Fasting and postprandial blood lipids and vascular function were assessed before and after 4 weeks of a pecan-enriched or nut-free diet. Daily pecan consumption for 4 weeks improved fasting and postprandial blood lipids and microvascular reactivity in older adults. Because changes in microvascular function typically precipitate macrovascular changes, long-term pecan consumption may improve vascular health and reduce risk for cardiovascular events. [Display omitted] [ABSTRACT FROM AUTHOR]

Purpose: We compared aerobic capacity ( V ˙ O 2 max ), mitochondrial capacity ( m V ˙ O 2 ), anaerobic power, strength, and muscle endurance in healthy, active men from strength (STR), endurance (END) and high-intensity functional training (HIFT) backgrounds. Methods: Twenty-four men (n = 8/group) completed a cycle ergometer test to determine V ˙ O 2 max , followed by a 3-min all-out test to determine peak (PP) and end power (EP), and to estimate anaerobic [work done above EP (WEP)] and aerobic work capacity. Strength was determined by knee extensor maximal voluntary contraction at various flexion angles. The endurance index (EI) of the vastus lateralis (VL) was assessed by measuring muscle contraction acceleration during electrical twitch mechanomyography. m V ˙ O 2 max of the VL was assessed using near-infrared spectroscopy to estimate muscle oxygen consumption during transient femoral artery occlusions. Results: V ˙ O 2 max was significantly different among groups (p <.05). PP was significantly higher in HIFT and STR versus END (p <.05). EP was significantly higher in HIFT and END compared to STR (p <.05). WEP was significantly higher in STR compared to END (p <.05), whereas total work done was significantly higher in HIFT and END compared to STR (p <.05). m V ˙ O 2 max and EI were comparable between HIFT and END but significantly lower in STR versus END (p <.05). Torque production was significantly lower in END compared to STR and HIFT at all flexion angles (p <.05), with no difference between STR and HIFT. Conclusion: HIFT participants can exert similar power outputs and absolute strength compared to strength focused participants but exhibit fatigue resistance and mitochondrial capacity comparable to those who train for endurance. [ABSTRACT FROM AUTHOR]

We aimed to determine if chronic endurance-exercise habits affected redox status and paracrine function of CD34+ and CD34-/CD31+ circulating angiogenic cells (CACs). Subjects were healthy, nonsmoking men and women aged 18-35 yr and categorized by chronic physical activity habits. Blood was drawn from each subject for isolation and culture of CD34+ and CD34-/CD31+ CACs. No differences in redox status were found in any group across either cell type. Conditioned media (CM) was generated from the cultured CACs and used in an in vitro human umbilical vein endothelial cell-based tube assay. CM from CD34+ cells from inactive individuals resulted in tube structures that were 29% shorter in length (P < 0.05) and 45% less complex (P < 0.05) than the endurance-trained group. CD34-/CD31+ CM from inactive subjects resulted in tube structures that were 26% shorter in length (P < 0.05) and 42% less complex (P < 0.05) than endurance-trained individuals. Proteomics analyses identified S100A8 and S100A9 in the CM. S100A9 levels were 103% higher (P < 0.05) and S100A8 was 97% higher in the CD34-/CD31+ CM of inactive subjects compared with their endurance-trained counterparts with no significant differences in either protein in the CM of CD34+ CACs as a function of training status. Recombinant S100A8/A9 treatment at concentrations detected in inactive subjects' CD34-/CD31+ CAC CM also reduced tube formation (P < 0.05). These findings are the first, to our knowledge, to demonstrate a differential paracrine role in CD34+ and CD34-/CD31+ CACs on tube formation as a function of chronic physical activity habits and identifies a differential secretion of S100A9 by CD34-/CD31+ CACs due to habitual exercise. [ABSTRACT FROM AUTHOR]

The progression in nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis is a serious health concern, but the underlying mechanisms remain unclear. We hypothesized that chronic inhibition of nitric oxide (NO) synthase (NOS) via Nω-nitro-L-arginine methyl ester (L-NAME) would intensify liver injury in a rat model of obesity, insulin resistance, and NAFLD. Obese Otsuka Long-Evans Tokushima fatty (OLETF) and lean Long-Evans Tokushima Otsuka (LETO) rats received control or L-NAME (65–70 mg·kg-1·day-1)-containing drinking water for 4 wk. L-NAME treatment significantly (P < 0.05) reduced serum NO metabolites and food intake in both groups. Remarkably, despite no increase in body weight, L-NAME treatment increased hepatic triacylglycerol content (+40%, P < 0.05) vs. control OLETF rats. This increase was associated with impaired (P < 0.05) hepatic mitochondrial state 3 respiration. Interestingly, the opposite effect was found in LETO rats, where L-NAME increased (P < 0.05) hepatic mitochondrial state 3 respiration. In addition, L-NAME induced a shift toward proinflammatory M1 macrophage polarity, as indicated by elevated hepatic CD11c (P < 0.05) and IL-1β (P = 0.07) mRNA in OLETF rats and reduced expression of the anti-inflammatory M2 markers CD163 and CD206 (P < 0.05) in LETO rats. Markers of total macrophage content (CD68 and F4/80) mRNA were unaffected by L-NAME in either group. In conclusion, systemic NOS inhibition in the obese OLETF rats reduced hepatic mitochondrial respiration, increased hepatic triacylglycerol accumulation, and increased hepatic inflammation. These findings suggest an important role for proper NO metabolism in the hepatic adaptation to obesity. [ABSTRACT FROM AUTHOR]

New Findings What is the central question of this study? Does endurance exercise training cause anti-atherogenic effects on the endothelium in a swine model of familial hypercholesterolaemia (FH), and how are these effects distributed across veins, arteries and multiple vascular territories within each system?, What is the main finding and its importance? Coronary artery endothelium-dependent vasomotor function was depressed in sedentary FH pigs compared with sedentary control animals, and exercise training did not change vasomotor function within FH. In systemic conduit arteries and veins, few effects of FH on endothelial cell protein expression were noted, including both pro- and anti-atherogenic changes. These findings suggest that exercise training does not produce a consistently improved endothelial cell phenotype in either coronary or systemic conduit vessels in this swine model of FH., Exercise training has emerged as an intervention for the primary and secondary prevention of coronary artery disease, but the mechanisms through which training reduces relative risk are not completely understood. The goal of this study was to investigate the impact of endurance exercise training on vasomotor function and vascular cell phenotype in coronary arteries and systemic conduit arteries and veins against a background of advanced atherosclerosis. We tested the hypothesis that exercise training restores endothelial vasomotor function and produces an anti-atherogenic endothelial and smooth muscle cell phenotype in familial hypercholesterolaemic (FH) swine. The study included 30 FH (15 exercised and 15 sedentary) and 13 non-FH control male castrated swine. The exercise-training intervention consisted of treadmill running 5 days per week for 16-20 weeks. Tissues sampled at sacrifice included vascular rings from the coronary circulation for vasomotor function experiments (dose-dependent bradykinin-induced vasorelaxation) and endothelial cells (ECs) from isolated segments of the thoracic aorta, the carotid, brachial, femoral and renal arteries, as well as each corresponding regionally associated vein, and from the abdominal vena cava, the right coronary and internal mammary arteries. Smooth muscle cells were sampled from the right coronary artery only. Vascular cell phenotype was assessed by immunoblotting for a host of both pro- and anti-atherogenic markers [e.g. endothelial nitric oxide synthase, p67phox, superoxide dismutase 1 (SOD1)]. Coronary artery endothelium-dependent vasomotor function was depressed in sedentary FH pigs compared with sedentary control pigs, and exercise training did not change vasomotor function within FH. In contrast, only scattered effects of FH on EC phenotype were noted across the vasculature, which included both pro- and anti-atherogenic changes in EC protein expression (e.g. increased endothelial nitric oxide synthase in carotid artery ECs, decreased p67phox in brachial artery ECs, but decreased expression of the antioxidant protein SOD1 in thoracic vena cava; all P < 0.05). In thoracic vena cava ECs, this deficit was corrected by exercise training, while no other effects of exercise were observed in conduit vessel EC phenotype. Thus, while exercise training abrogated the adverse effect of hypercholesterolaemia on thoracic vena cava SOD1 expression, it appears that exercise training does not produce a consistently improved EC phenotype in either coronary or systemic conduit vessels in this FH swine model. [ABSTRACT FROM AUTHOR]

L7484 --> 953.3 --> Background: High‐intensity functional training (HIFT) can play a major role in physiological adaptations to prevent cardiometabolic disease. A majority of HIFT interventions incorporate a CrossFit (CF) training methodology, in which the goal is to increase work capacity over time while using mono‐structural, body weight, and weightlifting movements. Methods: We measured aerobic capacity, metabolic response during high‐intensity interval exercise (HIIE), resting mitochondrial oxidative capacity, and resting large vessel function and microvascular reactivity in adults who have participated in a CF exercise for greater than one year vs. a sedentary group completing <2 h·wk‐1 of structure exercise for at least one year (SED). Results: 21 healthy, non‐smoking, participants were recruited (CF n = 13 vs. SED n = 8). CF participants had 40.4% greater absolute and 33.0% relative VO2 peak (P < 0.001) and lower body composition (CF = 18.6 (3.8) vs. SED = 30.3 (8.4); P < 0.001). CF participants had lower ratings of perceived exertion (P = 0.022) with higher respiratory responses (P < 0.05) and a lower heart rate response during HIIE (P = 0.024). CF participants had higher fat and carbohydrate oxidation when expressed as absolute and body weight relative values (P < 0.013), but not when expressed relative to lean mass (P > 0.200), indicating that skeletal muscle mass is a primary driver in substrate oxidation. CF participants had greater mitochondrial oxidative capacity (CF n = 12; P = 0.014). There were no differences in large artery function, but CF participants had greater baseline arterial diameter (CF n = 12; P = 0.004) and faster reperfusion following arterial occlusion (CF n = 12; P < 0.05), suggesting some influence of exercise habits on microvascular function. Conclusion: Overall, these data support the effectiveness of HIFT programs, like CF exercise, to improve fitness and weight status and metabolic, mitochondrial, and vascular function. [ABSTRACT FROM AUTHOR]

Objective To test the hypothesis that chronic metformin treatment enhances insulin-induced vasodilation in skeletal muscle resistance arteries and arterioles. Methods We assessed the effect of metformin treatment (from 20 to 32 weeks of age) of obese Otsuka Long Evans Tokushima Fatty ( OLETF) rats and lean LETO rats (300 mg/kg) on insulin-stimulated vasodilation in isolated skeletal muscle feed arteries and arterioles. Results Metformin treatment significantly lowered food intake, body weight, percent body fat, and HbA1c in OLETF rats. Metformin resulted in a ~30% reduction in insulin-induced vasodilation of soleus feed arteries ( SFA) from OLETF rats. Inhibition of endothelin-1 ( ET-1) signaling produced 20% dilation and eliminated the difference between metformin-treated and untreated OLETF rats in insulin-induced dilation of SFA. In contrast to the SFA, metformin did not alter insulin-stimulated vasodilation in gastrocnemius feed arteries ( GFA), or second-order arterioles in the red (G2A-R) or white (G2A-W) portions of the gastrocnemius muscle of OLETF rats. Metformin had no effects on vasomotor responses of arteries from LETO. Conclusions Although metformin exerts favorable effects on body composition and HbA1c, it does not enhance the vasodilatory responses to insulin in the skeletal muscle feed arteries or arterioles of the obese OLETF rat. [ABSTRACT FROM AUTHOR]

BACKGROUND: Pecans are rich in nutrients known to benefit cognition. OBJECTIVE: To examine the effect of daily pecan consumption on cognitive function in older adults. METHODS: In this randomized controlled trial, 42 adults (50–75y) either consumed 68 g of pecans/day for 4-weeks (pecan; n = 21) or avoided all nuts (control; n = 21). At pre- (V1) and post-intervention (V2) visits, cognitive function was assessed using a fluid composite score and four subtests from the NIH Toolbox-Cognitive Battery (NIHTB-CB) (Flanker Test, Digital Change Card Sort Test (DCCS), Picture Sequence Memory Test (PSMT), NIHTB Auditory Verbal Learning Test (RAVLT)) at fasting, 30- and 210-min after a high-saturated fat meal void of pecans. RESULTS: From V1 to V2, fasting and postprandial cognitive performance did not differ between groups. There were improvements in both groups for fasting fluid composite score (p < 0.001) and performance on RAVLT, PSMT, DCCS, and Flanker tests from V1 to V2 (p < 0.001 for all), with no differences between groups. Additionally, postprandial performance on RAVLT, PSMT, and Flanker tests improved at V2 (p < 0.01 for each), with no differences between groups. CONCLUSIONS: A short-term pecan-enriched diet did not provide additional cognitive benefits in healthy older adults in the fasted or postprandial state. [ABSTRACT FROM AUTHOR]

The purpose of this systematic review was to synthesize and evaluate current literature examining the effects of exercise on postprandial fat oxidation, as well as to provide future direction. A quantitative review was performed using meta-analytic methods. A moderator analysis was performed to investigate potential variables that could influence the effect of exercise on postprandial fat oxidation. Fifty-six effects from 26 studies were retrieved. There was a moderate effect of exercise on postprandial fat oxidation (Cohen's d = 0.58 (95% CI, 0.39 to 0.78)). Moderator analysis revealed that sex, age, weight status, training status, exercise type, exercise intensity, timing of exercise, and composition of the meal challenge significantly affected the impact of prior exercise on postprandial fat oxidation. The moderator analysis also indicated that most previous studies have investigated the impact of prior moderate-intensity endurance exercise on postprandial fat oxidation in young, healthy, lean men. Suggested priorities for future research in this area include (i) an examination of sex differences in and/or female-specific aspects of postprandial metabolism; (ii) a comprehensive evaluation of exercise modalities, intensities, and durations; and (iii) a wider variety of test meal compositions, especially those with higher fat content. Novelty A systematic review of the impact of exercise on postprandial fat oxidation was performed using meta-analytic methods. Analysis revealed a moderate effect of exercise on postprandial fat oxidation. The presented data support a need for future studies to investigate sex differences and to include comprehensive evaluations of exercise modalities, intensities, and duration. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?What are the metabolic impacts of high intensity functional Tabata exercise?What is the main finding and its importance?Tabata exercise with high intensity functional movements causes increases in fasted and postprandial fat oxidation the day after exercise without altering postprandial triglyceride concentrations. These results support the usage of a Tabata‐style high intensity functional exercise to improve postprandial fat oxidation. We evaluated the effect of a high fat meal with and without prior high intensity functional exercise executed in a Tabata‐style interval pattern on resting and postprandial substrate oxidation, as well as postprandial blood glucose and triglyceride concentrations. Eleven healthy males completed two trials (Tabata exercise (TE) and non‐exercise control (CON)) in random order separated by 7 days. A two‐day protocol was used in which TE or CON was performed on the first day and a high fat meal was administered ∼13 h later the following morning. Power output from the TE session was quantified using a kinematic approach by calculating external work performed per unit time for each of the four exercises (rowing, dumbbell thrusters, kettlebell swings and burpees). For the meal challenge, respiratory gases and blood samples were taken fasted and at 1, 2 and 3 h postprandial. Fat oxidation was significantly higher after TE compared to CON at all time points (P < 0.05). Carbohydrate oxidation was significantly lower after TE compared to CON at 1 h postprandial (P < 0.05). There were no significant effects of TE on fasting or postprandial glucose or triglyceride concentrations. Functional exercises performed in a high intensity TE pattern enhance fasting and postprandial fat oxidation on the following day with minimal influence on blood triglycerides or glucose levels. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study? What is the effect of exercise intensity on circulating microparticle populations in young, healthy men and women? What is the main finding and its importance? Acute, moderate‐intensity continuous exercise and high‐intensity interval exercise altered distinct microparticle populations during and after exercise in addition to a sex‐specific response in CD62E+ microparticles. The microparticles studied contribute to cardiovascular disease progression, regulate vascular function and facilitate new blood vessel formation. Thus, characterizing the impact of intensity on exercise‐induced microparticle responses advances our understanding of potential mechanisms underlying the beneficial vascular adaptations to exercise. Abstract: Circulating microparticles (MPs) are biological vectors of information within the cardiovascular system that elicit both deleterious and beneficial effects on the vasculature. Acute exercise has been shown to alter MP concentrations, probably through a shear stress‐dependent mechanism, but evidence is limited. Therefore, we investigated the effect of exercise intensity on plasma levels of CD34+ and CD62E+ MPs in young, healthy men and women. Blood samples were collected before, during and after two energy‐matched bouts of acute treadmill exercise: interval exercise (10 × 1 min intervals at ∼95% of maximal oxygen uptake V ̇ O 2 max) and continuous exercise (65% V ̇ O 2 max). Continuous exercise, but not interval exercise, reduced CD62E+ MP concentrations in men and women by 18% immediately after exercise (from 914.5 ± 589.6 to 754.4 ± 390.5 MPs μl−1; P < 0.05), suggesting that mechanisms underlying exercise‐induced CD62E+ MP dynamics are intensity dependent. Furthermore, continuous exercise reduced CD62E+ MPs in women by 19% (from 1030.6 ± 688.1 to 829.9 ± 435.4 MPs μl−1; P < 0.05), but not in men. Although interval exercise did not alter CD62E+ MPs per se, the concentrations after interval exercise were higher than those observed after continuous exercise (P < 0.05). Conversely, CD34+ MPs did not fluctuate in response to short‐duration acute continuous or interval exercise in men or women. Our results suggest that exercise‐induced MP alterations are intensity dependent and sex specific and impact MP populations differentially. [ABSTRACT FROM AUTHOR]

Aims: Type 2 diabetes treatment primarily focuses on reducing hyperglycemia, including postprandial glucose excursions. Hypoglycemic agents are used clinically to lower fasting and postprandial glucose. Metformin is the first-line therapy; however, if metformin is inadequate then 'add-on' hypoglycemic agents are implemented. Postmeal exercise has been shown to lower postprandial glucose. The aim of this study was to assess if postmeal exercise provides additional glucose-lowering benefit, beyond medication alone, in those on add-on hypoglycemic agents.Methods: Postprandial glucose excursions in eight participants with type 2 diabetes (Age: 60±10.7, HbA1C: 7.9±2.3) being treated with add-on hypoglycemic agents were assessed during both drug-treated sedentary and drug-treated postmeal exercise conditions. Continuous glucose monitoring was used to assess peak and area under the glucose curve (AUC) during exercise, as well as peak within a 2-h time window, 2-h total and 2-h incremental AUC after a standardized breakfast meal. Postmeal exercise consisted of 3×10-min intervals of treadmill walking at 50% maximal oxygen uptake.Results: Glucose peak (drug only: 13.8±3.7, drug/exercise: 9.9±2.7mmol/L; p=0.02) and AUC (drug only: 500±136, drug/exercise: 357±89mmol/L×40min; p=0.03) were reduced during postmeal exercise. Breakfast 2-h incremental AUC was also reduced (drug only: 585±291, drug/exercise: 330±294; p=0.047).Discussion: Post-breakfast exercise lowered glucose during the exercise bout, although this effect was not sustained on later meals. [ABSTRACT FROM AUTHOR]

We tested the hypothesis that a 6-week regimen of simvastatin would attenuate skeletal muscle adaptation to low-intensity exercise. Male C57BL/6J wildtype mice were subjected to 6-weeks of voluntary wheel running or normal cage activities with or without simvastatin treatment (20 mg/kg/d, n = 7–8 per group). Adaptations in in vivo fatigue resistance were determined by a treadmill running test, and by ankle plantarflexor contractile assessment. The tibialis anterior, gastrocnemius, and plantaris muscles were evaluated for exercised-induced mitochondrial adaptations (i.e., biogenesis, function, autophagy). There was no difference in weekly wheel running distance between control and simvastatin-treated mice (P = 0.51). Trained mice had greater treadmill running distance (296%, P<0.001), and ankle plantarflexor contractile fatigue resistance (9%, P<0.05) compared to sedentary mice, independent of simvastatin treatment. At the cellular level, trained mice had greater mitochondrial biogenesis (e.g., ~2-fold greater PGC1α expression, P<0.05) and mitochondrial content (e.g., 25% greater citrate synthase activity, P<0.05), independent of simvastatin treatment. Mitochondrial autophagy-related protein contents were greater in trained mice (e.g., 40% greater Bnip3, P<0.05), independent of simvastatin treatment. However, Drp1, a marker of mitochondrial fission, was less in simvastatin treated mice, independent of exercise training, and there was a significant interaction between training and statin treatment (P<0.022) for LC3-II protein content, a marker of autophagy flux. These data indicate that whole body and skeletal muscle adaptations to endurance exercise training are attainable with simvastatin treatment, but simvastatin may have side effects on muscle mitochondrial maintenance via autophagy, which could have long-term implications on muscle health. [ABSTRACT FROM AUTHOR]

Purpose: Circulating angiogenic cells (CAC) comprise multiple subpopulations of exercise-inducible peripheral blood mononuclear cells (PBMC) that promote angiogenesis and maintain endothelial integrity. We examined the effect of acute maximal exercise on CD31+, CD62E+, CD14+/ CD31+, CD34+/VEGFR2+, CD3+/CD31+, and CD3+ PBMC in young, healthy adults. Methods: Blood samples were collected before and immediately after a graded treadmill exercise test for CAC analysis via flow cytometry. Results: Maximal exercised produced 40%, 29%, 33%, 14%, and 33% increases in lymphocytic CD31+, monolymphocytic CD31+, CD62E+, CD14+/CD31+, and CD34+/VEGFR2+ PBMC, respectively (P < 0.05). CD3+/CD31+ and CD3+ cells were not altered with exercise. CD62E+ and CD14+/CD31+ PBMC were selectively augmented in women by 54% and 20%, respectively (P < 0.05). Exploratory analyses indicated that maximal exercise induced greater increases in CD62E+ and CD14+/CD31+ PBMC among women in the luteal phase compared with those in the follicular phase (P < 0.05). Basal lymphocytic PBMC and postexercise lymphocytic and monolymphocytic CD31+ PBMC were lower among contraceptive users than nonusers. Conclusions: Maximal exercise induces a robust CAC response encompassing both progenitor and nonprogenitor cell types, with these effects differing between men and women for CD62E+ and CD14+/CD31+ cell types and the potential influence of menstrual cycle phase and contraceptive use. [ABSTRACT FROM AUTHOR]

Key points Reducing excessive oxidative stress, through chronic exercise or antioxidants, can decrease the negative effects induced by excessive amounts of oxidative stress. Transient increases in oxidative stress produced during acute exercise facilitate beneficial vascular training adaptations, but the effects of non-specific antioxidants on exercise training-induced vascular adaptations remain elusive., Circulating angiogenic cells (CACs) are an exercise-inducible subset of white blood cells that maintain vascular integrity., We investigated whether mitochondria-specific antioxidant (MitoQ) supplementation would affect the response to 3 weeks of endurance exercise training in CACs, muscle mitochondrial capacity and maximal oxygen uptake in young healthy men., We show that endurance exercise training increases multiple CAC types, an adaptation that is not altered by MitoQ supplementation. Additionally, MitoQ does not affect skeletal muscle or whole-body aerobic adaptations to exercise training., These results indicate that MitoQ supplementation neither enhances nor attenuates endurance training adaptations in young healthy men., Abstract Antioxidants have been shown to improve endothelial function and cardiovascular outcomes. However, the effects of antioxidants on exercise training-induced vascular adaptations remain elusive. General acting antioxidants combined with exercise have not impacted circulating angiogenic cells (CACs). We investigated whether mitochondria-specific antioxidant (MitoQ) supplementation would affect the response to 3 weeks of endurance exercise training on CD3+, CD3+/CD31+, CD14+/CD31+, CD31+, CD34+/VEGFR2+ and CD62E+ peripheral blood mononuclear cells (PBMCs), muscle mitochondrial capacity, and maximal oxygen uptake ( [ABSTRACT FROM AUTHOR]

Endothelial dysfunction and inflammation are characteristics of subclinical atherosclerosis and may increase through progressive menopausal stages. Evaluating endothelial responses to acute exercise can reveal underlying dysfunction not apparent in resting conditions. The purpose of this study was to investigate markers of endothelial function and inflammation before and after acute exercise in healthy low-active perimenopausal (PERI) and late postmenopausal (POST) women. Flow-mediated dilation (FMD), CD31+/CD42b- and CD62E+ endothelial microparticles (EMPs), and the circulating inflammatory factors monocyte chemoattractant protein 1 (MCP-1), interleukin 8 (IL-8), and tumor necrosis factor-α (TNF-α) were measured before and 30 min after acute exercise. Before exercise, FMD was not different between groups (PERI: 6.4 ± 0.9% vs. POST: 6.5 ± 0.8%, P = 0.97); however, after acute exercise PERI tended to improve FMD (8.5 ± 0.9%, P = 0.09), whereas POST did not (6.2 ± 0.8%, P = 0.77). Independent of exercise, we observed transient endothelial dysfunction in POST with repeated FMD measures. There was a group × exercise interaction for CD31+/CD42b- EMPs (P = 0.04), where CD31+/CD42b- EMPs were similar before exercise (PERI: 57.0 ± 6.7 EMPs/µl vs. POST: 58.5 ± 5.3 EMPs/µl, P = 0.86) but were higher in POST following exercise (PERI: 48.2 ± 6.7 EMPs/µl vs. POST: 69.4 ± 5.3 EMPs/µl, P = 0.023). CD62E+ EMPs were lower in PERI compared with POST before exercise (P < 0.001) and increased in PERI (P = 0.04) but did not change in POST (P = 0.68) in response to acute exercise. After acute exercise, MCP-1 (P = 0.055), TNF-α (P = 0.02), and IL-8 (P < 0.001) were lower in PERI but only IL-8 decreased in POST (P < 0.001). Overall, these data suggest that perimenopausal and late postmenopausal women display different endothelial and inflammatory responses to acute exercise. [ABSTRACT FROM AUTHOR]

Subpopulations of peripheral blood mononuclear cells (PMBCs), known as circulating angiogenic cells (CACs), have been implicated in endothelial repair, angiogenesis and vascular homeostasis. Conversely, microparticles released from endothelial cells, platelets and leucocytes in response to injury or apoptosis are elevated in chronic diseases. We investigated the effect of acute exercise on CAC subpopulations, specifically CD34+/VEGFR2+, CD3+/CD31+, CD14+/CD31+ and CD62E+ PBMCs and CD62E+, CD31+/CD42b- and CD34+ MPs in men and women. Additionally, we examined angiogenesis-related gene expression in CD34+, CD31+ and CD62E+ PBMCs at baseline and after exercise. Finally, we examined whether acute exercisemodulates CD62E+ PBMC paracrine actions on cultured endothelial cells. Blood samples for CAC and MP analyses were obtained before and after cycling exercise at 70% peak oxygen uptake that elicited an energy expenditure of 600 kcal. Exercise produced a decrease in CD14+/CD31+ PBMCs, whereas CD62E expression on PBMCs increased with exercise. CD34+/VEGFR2+ and CD3+/CD31+ PBMC levels were not altered with exercise. Gene expression analysis revealed amore proangiogenic phenotype in CD62E+ cells at baseline compared with CD31+ and CD34+ cells. Conditioned media from CD62E+ PBMCs obtained after exercise exerted a proangiogenic influence on human umbilical vein endothelial cells, with increases in genes encoding receptors for growth factors (KDR, FGFR1 and EGFR) and inflammatory mediators (TLR4 and TNFR1). Finally, exercise increased CD62E+ endothelial MPs in men and increased CD34+ MPs in women. Our work highlights the potential role of CD62E+ cells as a novel, exercise-responsive proangiogenic cell population and demonstrates sex-specific exercise-induced changes in circulatingMPs. [ABSTRACT FROM AUTHOR]

Ovariectomized rodents model human menopause in that they rapidly gain weight, reduce spontaneous physical activity (SPA), and develop metabolic dysfunction, including insulin resistance. How contrasting aerobic fitness levels impacts ovariectomy (OVX)-associated metabolic dysfunction is not known. Female rats selectively bred for high and low intrinsic aerobic fitness [high-capacity runners (HCR) and low-capacity runners (LCR), respectively] were maintained under sedentary conditions for 39 wk. Midway through the observation period, OVX or sham (SHM) operations were performed providing HCR-SHM, HCR-OVX, LCR-SHM, and LCR-OVX groups. Glucose tolerance, energy expenditure, and SPA were measured before and 4 wk after surgery, while body composition via dual-energy X-ray absorptiometry and adipose tissue distribution, brown adipose tissue (BAT), and skeletal muscle phenotype, hepatic lipid content, insulin resistance via homeostatic assessment model of insulin resistance and AdipoIR, and blood lipids were assessed at death. Remarkably, HCR were protected from OVX-associated increases in adiposity and insulin resistance, observed only in LCR. HCR rats were ~30% smaller, had ~10% greater spontaneous physical activity (SPA), consumed ~ 10% more relative energy, had greater skeletal muscle proliferator-activated receptor coactivator 1-alpha, and ~40% more BAT. OVX did not increase energy intake and reduced SPA to the same extent in both HCR and LCR. LCR were particularly affected by an OVX-associated reduction in resting energy expenditure and experienced a reduction in relative BAT; resting energy expenditure correlated positively with BAT across all animals (r = 0.6; P < 0.001). In conclusion, despite reduced SPA following OVX, high intrinsic aerobic fitness protects against OVX-associated increases in adiposity and insulin resistance. The mechanism may involve preservation of resting energy expenditure. [ABSTRACT FROM AUTHOR]

Background: An acute bout of exercise can improve endothelial function and insulin sensitivity when measured on the day following exercise. Our aim was to compare acute high-intensity continuous exercise (HICE) to high-intensity interval exercise (HIIE) on circulating endothelial microparticles (EMPs) and insulin sensitivity in overweight/obese men and women. Methods: Inactive males (BMI = 30 ± 3, 25 ± 6 yr, n = 6) and females (BMI = 28 ± 2, 21 ± 3 yr, n = 7) participated in three experimental trials in a randomized counterbalanced crossover design: 1) No exercise control (Control); 2) HICE (20 min cycling @ just above ventilatory threshold); 3) HIIE (10 X 1-min @ ∼90% peak aerobic power). Exercise conditions were matched for external work and diet was controlled post-exercise. Fasting blood samples were obtained ∼18 hr after each condition. CD62E+ and CD31+/CD42b- EMPs were assessed by flow cytometry and insulin resistance (IR) was estimated by homeostasis model assessment (HOMA-IR). Results: There was a significant sex X exercise interaction for CD62E+ EMPs, CD31+/CD42b- EMPs, and HOMA-IR (all P<0.05). In males, both HICE and HIIE reduced EMPs compared to Control (P≤0.05). In females, HICE increased CD62E+ EMPs (P<0.05 vs. Control) whereas CD31+/CD42b- EMPs were unaltered by either exercise type. There was a significant increase in HOMA-IR in males but a decrease in females following HIIE compared to Control (P<0.05). Conclusions: Overweight/obese males and females appear to respond differently to acute bouts of high-intensity exercise. A single session of HICE and HIIE reduced circulating EMPs measured on the morning following exercise in males but in females CD62E+ EMPs were increased following HICE. Next day HOMA-IR paradoxically increased in males but was reduced in females following HIIE. Future research is needed to investigate mechanisms responsible for potential differential responses between males and females. [ABSTRACT FROM AUTHOR]

We recently developed a clinically relevant mini-swine model of heart failure with preserved ejection fraction (HFpEF), in which diastolic dysfunction was associated with increased mitochondrial permeability transition (MPT). Early diastolic function is ATP and Ca2+-dependent, thus, we hypothesized chronic low doses of cyclosporine (CsA) would preserve mitochondrial function via inhibition of MPT and subsequently maintain normal cardiomyocyte Ca2+ handling and contractile characteristics. Left ventricular cardiomyocytes were isolated from aortic-banded Yucatan mini-swine divided into three groups; control nonbanded (CON), HFpEF nontreated (HF), and HFpEF treated with CsA (HF-CsA). CsA mitigated the deterioration of mitochondrial function observed in HF animals, including functional uncoupling of Complex I-dependent mitochondrial respiration and increased susceptibility to MPT. Attenuation of mitochondrial dysfunction in the HF-CsA group was not associated with commensurate improvement in cardiomyocyte Ca2+ handling or contractility. Ca2+ transient amplitude was reduced and transient time to peak and recovery (tau) prolonged in HF and HF-CsA groups compared to CON. Alterations in Ca2+ transient parameters observed in the HF and HF-CsA groups were associated with decreased cardiomyocyte shortening and shortening rate. Cellular function was consistent with impaired in vivo systolic and diastolic whole heart function. A significant systemic hypertensive response to CsA was observed in HF-CsA animals, and may have played a role in the accelerated the development of heart failure at both the whole heart and cellular levels. Given the significant detriment to cardiac function observed in response to CsA, our findings suggest chronic CsA treatment is not a viable therapeutic option for HFpEF. [ABSTRACT FROM AUTHOR]

To better understand the impact of childhood obesity on intra-abdominal adipose tissue phenotype, a complete transcriptomic analysis using deep RNA-sequencing (RNA-seq) was performed on omental adipose tissue (OMAT) obtained from lean and Western diet-induced obese juvenile Ossabaw swine. Obese animals had 88% greater body mass, 49% greater body fat content, and a 60% increase in OMAT adipocyte area (all P < 0.05) compared with lean pigs. RNA-seq revealed a 37% increase in the total transcript number in the OMAT of obese pigs. Ingenuity Pathway Analysis showed transcripts in obese OMAT were primarily enriched in the following categories: 1) development, 2) cellular function and maintenance, and 3) connective tissue development and function, while transcripts associated with RNA posttranslational modification, lipid metabolism, and small molecule biochemistry were reduced. DAVID and Gene Ontology analyses showed that many of the classically recognized gene pathways associated with adipose tissue dysfunction in obese adults including hypoxia, inflammation, angiogenesis were not altered in OMAT in our model. The current study indicates that obesity in juvenile Ossabaw swine is characterized by increases in overall OMAT transcript number and provides novel data describing early transcriptomic alterations that occur in response to excess caloric intake in visceral adipose tissue in a pig model of childhood obesity. [ABSTRACT FROM AUTHOR]

Physical activity- induced prevention of hepatic steatosis is maintained during shortterm (7-day) transitions to an inactive state; however, whether these protective effects are present under a longer duration of physical inactivity is largely unknown. Here, we sought to determine whether previous physical activity had protective effects on hepatic steatosis and metabolic health following 4 wk of physical inactivity. Four-week old, hyperphagic, male Otsuka Long-Evans Tokushima fatty (OLETF) rats were randomly assigned to either a sedentary group for 16 wk (OLETF-SED), given access to running wheels for 16 wk with wheels locked 5 h (OLETF-WL5hr) or given access to running wheels for 12 wk with wheels locked 4 wk (OLETF-WL4wk) prior to death. Four weeks of physical inactivity caused hepatic steatosis development, but liver triglycerides remained 60% lower than OLETF-SED (P < 0.01), and this was associated with only a partial loss in activity-induced improvements in body composition, serum lipids, and glycemic control. Total hepatic mitochondrial palmitate oxidation, citrate synthase, and β-HAD activity returned to SED levels following 4 wk of inactivity, whereas markers of fatty acid uptake and lipogenesis remained relatively suppressed following 4 wk of inactivity. In addition, 4 wk of inactivity caused a complete loss of activity-induced increases in serum IL-6 and reductions in regulated upon activation, normal T-cell expressed, and secreted (RANTES), and a partial loss in reductions in leptin, monocyte chemoattractant protein-1, and TNF-α. In conclusion, 4 wk of physical inactivity does not result in a complete loss in physical activity-induced benefits but does cause deterioration in the liver phenotype and overall metabolic health in hyperphagic OLETF rats. [ABSTRACT FROM AUTHOR]

According to the latest data from the Center for Disease Control and Prevention 17%, or 12.5 million, of children and adolescents aged 2-19 years in the United States are obese. Physical inactivity is designated as one of the actual causes of US deaths and undoubtedly contributes to the obesity epidemic in children and adults. Examining the effects of inactivity on physiological homeostasis during youth is crucial given that 58% of children between the ages 6-11 yr old fail to obtain the recommended 60 min/day of physical activity and 92% of adolescents fail to achieve this goal [Troiano et al. Med Sci Sports Exerc. 40, 2008]. Nonetheless, invasive mechanistic studies in children linking diminished physical activity with metabolic maladies are lacking for obvious ethical reasons. The rodent wheel lock (WL) model was adopted by our laboratory and others to study how different organ systems of juvenile rats respond to a cessation of daily physical activity. Our WL model houses rats in cages equipped with voluntary running wheels starting at 28 days of age. After a certain period of voluntary running (3 to 6 wk), the wheels are locked, thus preventing the rats' primary source of physical activity. The studies discussed herein suggest that obesity-associated maladies including skeletal muscle insulin resistance, hypothalamic leptin resistance, fatty acid oxidation impairments in skeletal muscle and adipose tissue, nonalcoholic fatty liver disease, and endothelial dysfunction are initiated in juvenile animals that are restrained from voluntary exercise via WL. The use of the juvenile rodent WL or other inactivity models will continue to provide a powerful clinical translational tool that can be used for primordial prevention of human childhood obesity. [ABSTRACT FROM AUTHOR]

Background: Individuals differ in the response to regular exercise. Whether there are people who experience adverse changes in cardiovascular and diabetes risk factors has never been addressed. Methodology/Principal Findings: An adverse response is defined as an exercise-induced change that worsens a risk factor beyond measurement error and expected day-to-day variation. Sixty subjects were measured three times over a period of three weeks, and variation in resting systolic blood pressure (SBP) and in fasting plasma HDL-cholesterol (HDL-C), triglycerides (TG), and insulin (FI) was quantified. The technical error (TE) defined as the within-subject standard deviation derived from these measurements was computed. An adverse response for a given risk factor was defined as a change that was at least two TEs away from no change but in an adverse direction. Thus an adverse response was recorded if an increase reached 10 mm Hg or more for SBP, 0.42 mmol/L or more for TG, or 24 pmol/L or more for FI or if a decrease reached 0.12 mmol/L or more for HDL-C. Completers from six exercise studies were used in the present analysis: Whites (N = 473) and Blacks (N = 250) from the HERITAGE Family Study; Whites and Blacks from DREW (N = 326), from INFLAME (N = 70), and from STRRIDE (N = 303); and Whites from a University of Maryland cohort (N = 160) and from a University of Jyvaskyla study (N = 105), for a total of 1,687 men and women. Using the above definitions, 126 subjects (8.4%) had an adverse change in FI. Numbers of adverse responders reached 12.2% for SBP, 10.4% for TG, and 13.3% for HDL-C. About 7% of participants experienced adverse responses in two or more risk factors. Conclusions/Significance: Adverse responses to regular exercise in cardiovascular and diabetes risk factors occur. Identifying the predictors of such unwarranted responses and how to prevent them will provide the foundation for personalized exercise prescription. [ABSTRACT FROM AUTHOR]