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Skeletal muscle microvascular blood flow (MBF) plays an important role in glucose disposal in muscle. Impairments in muscle MBF contribute to insulin resistance and prediabetes. Animal studies show that short-term (3 day) high-fat feeding blunts skeletal muscle MBF before impairing insulin-stimulated glucose disposal. It is not known whether this occurs in humans. We investigated the temporal impact of a 7-day high-calorie high-fat (HCHF) diet intervention ( þ 52% kJ; 41% fat) on fasting and postprandial cardiometabolic outcomes in 14 healthy adults (18-37 yr). Metabolic health and vascular responses to a mixed-meal challenge (MMC) were measured at pre (day 0)-, mid (day 4)- and post (day 8)-intervention. There were no significant differences in body weight, body fat %, fasting blood glucose, and fasting plasma insulin concentrations at pre-, mid- and postintervention. Compared with preintervention there was a significant increase in insulin (but not glucose) total area under the curve in response to the MMC at midintervention (P = 0.041) and at postintervention (P ¼ 0.028). Unlike at pre- and midintervention, at postintervention muscle MBF decreased at 60 min (P = 0.024) and 120 min (P = 0.023) after the MMC. However, macrovascular blood flow was significantly increased from 0 to 60 min (P < 0.001) and 120 min (P < 0.001) after the MMC at pre-, mid- and postintervention. Therefore, short-term HCHF feeding in healthy individuals leads to elevated postprandial insulin but not glucose levels and a blunting of meal-induced skeletal muscle MBF responses but not macrovascular blood flow responses. NEW & NOTEWORTHY This is the first study to investigate skeletal muscle microvascular blood flow (MBF) responses in humans after short-term high-calorie high-fat (HCHF) diet. The main findings were that HCHF diet causes elevated postprandial insulin in healthy individuals within 3 days and blunts meal-induced muscle MBF within 7 days, despite no impairments in postprandial glucose or macrovascular blood flow. [ABSTRACT FROM AUTHOR]

Adipose tissue microvascular blood flow (MBF) is stimulated postprandially to augment delivery of nutrients and hormones to adipocytes. Adipose tissue MBF is impaired in type 2 diabetes (T2D). Whether healthy individuals at-risk of T2D show similar impairments is unknown. We aimed to determine whether adipose tissue MBF is impaired in apparently healthy individuals with a family history of T2D. Overnight-fasted individuals with no family history of T2D for two generations (FH-, n = 13), with at least one parent with T2D (FH+, n = 14) and clinically diagnosed T2D (n = 11) underwent a mixed meal challenge (MMC). Metabolic responses [blood glucose, plasma insulin, plasma nonesterified fatty acids (NEFAs), and fat oxidation] were measured before and during the MMC. MBF in truncal subcutaneous adipose tissue was assessed by contrast ultrasound while fasting and 60 min post-MMC. FHþ had normal blood glucoses, increased adiposity, and impaired post-MMC adipose tissue MBF (Δ0.70 ± 0.22 vs. 2.45 ± 0.60 acoustic intensity/s, P = 0.007) and post-MMC adipose tissue insulin resistance (Adipo-IR index; Δ45.5 ± 13.9 vs. 7.8 ± 5.1 mmol/L × pmol/L, P = 0.007) compared with FH-. FH+ and T2D had an impaired ability to suppress fat oxidation post-MMC. Fat oxidation incremental area under the curve (iAUC) (35-55 min post-MMC, iAUC) was higher in FH+ and T2D than in FH- (P = 0.005 and 0.009, respectively). Postprandial MBF was negatively associated with postprandial fat oxidation iAUC (P = 0.01). We conclude that apparently healthy FH+ individuals display blunted postprandial adipose tissue MBF that occurs in parallel with adipose tissue insulin resistance and impaired suppression of fat oxidation, which may help explain their heightened risk for developing T2D. [ABSTRACT FROM AUTHOR]

Aging skeletal muscle shows an increased time to peak force and relaxation and a decreased specific force, all of which could relate to changes in muscle [Ca.sup.2+] handling. The purpose of this study was to determine if [Ca.sup.2+]-handling protein content and function are decreased in senescent gastrocnemius muscle and if initiating a training program in late middle age (LMA, 29 mo old) could improve function in senescent (34-to 36-mo-old) muscle. LMA male Fischer 344 x Brown-Norway rats underwent 5-7 mo of treadmill training. Aging resulted in a decrease in maximal sarco(endo)plasmic reticulum [Ca.sup.2+]-ATPase (SERCA) activity and a decrease in [Ca.sup.2+] release rate but no change in [Ca.sup.2+] uptake rate. Efficiency of the [Ca.sup.2+] pump was increased with age, as was the content of SERCA2a. Training caused a further increase in SERCA2a content. Aging also caused an increase in protein carbonyl and reactive nitrogen species damage accumulation, and both further increased with training. Consistent with the increase in oxidative damage, heat shock protein 70 content was increased with age and further increased with training. Together, these results suggest that while initiating exercise training in LMA augments the age-related increase in expression of heat shock protein 70 and the more efficient SERCA2a isoform, it did not prevent the decrease in SERCA activity and exacerbated oxidative damage in senescent gastrocnemius muscle. aging; sarcoplasmic reticulum; nitrotyrosine; carbonylation; endurance training doi: 10.1152/ajpregu.00663.2009.

We previously showed that 7 wk of treadmill exercise training in late-middle-aged rats can reverse the modest reductions in skeletal muscle aerobic function and enzyme activity relative to values in young adult rats (Exp Physiol 93: 863-871, 2008). The purpose of the present study was to determine whether extending this training program into senescence would attenuate the accelerated decline in the muscle aerobic machinery normally seen at this advanced age. For this purpose, 29-mo-old Fisher 344 Brown-Norway rats underwent 5 or 7 mo of treadmill exercise training. Training resulted in greater exercise capacity during an incremental treadmill exercise test and reduced percent body fat in 34- and 36-mo-old rats and improved survival. Despite these benefits at the whole body level, in situ muscle aerobic capacity and muscle mass were not greater in the trained groups at 34 mo or 36 mo of age. Similarly, the trained groups did not have higher activities of citrate synthase (CS) or Complex IV in homogenates of either the plantaris (fast twitch) or the soleus (slow twitch) muscles at either age. Finally, protein expression of CS (a marker of mitochondrial content) and peroxisome proliferator-activated receptor-[gamma] coactivator-1 (relating to the drive on mitochondrial biogenesis) were not higher in the trained groups. Therefore, although treadmill training from late middle age into senescence had significant benefits on running capacity, survival, and body fat, it did not prevent the declines in muscle mass, muscle aerobic capacity, or mitochondrial enzyme activities normally seen across this age, revealing a markedly diminished plasticity of the aerobic machinery in response to endurance exercise at advanced age. aging; oxygen uptake; sarcopenia; mitochondria; endurance training

Background: There is a universal need to increase the number of adults meeting physical activity (PA) recommendations to help improve health. In recent years, electrically assisted bicycles (e‐bikes) have emerged as a promising method for supporting people to initiate and maintain physical activity levels. To the best of our knowledge, there have been no meta‐analyses conducted to quantify the difference in physiological responses between e‐cycling with electrical assistance, e‐cycling without assistance, conventional cycling, and walking. Methods: A systematic review and meta‐analysis was conducted following PRISMA guidelines. We identified short‐term e‐bike studies, which utilized a crossover design comparing physiological outcomes when e‐cycling with electrical assistance, e‐cycling without electrical assistance, conventional cycling, or walking. Energy expenditure (EE), heart rate (HR), oxygen consumption (VO2), power output (PO), and metabolic equivalents (METs) outcomes were included within the meta‐analysis. Results: Fourteen studies met our inclusion criteria (N = 239). E‐cycling with electrical assistance resulted in a lower energy expenditure (EE) [SMD = −0.46 (−0.98, 0.06), p = 0.08], heart rate (HR) [MD = −11.41 (−17.15, −5.68), p < 0.000, beats per minute], oxygen uptake (VO2) [SMD = −0.57 (−0.96, −0.17), p = 0.005], power output (PO) [MD = −31.19 (−47.19 to −15.18), p = 0.000, Watts], and metabolic equivalent (MET) response [MD = −0.83 (−1.52, −0.14), p = 0.02, METs], compared with conventional cycling. E‐cycling with moderate electrical assistance resulted in a greater HR response [MD 10.38 (−1.48, 22.23) p = 0.09, beats per minute], and VO2 response [SMD 0.34 (−0.14, 0.82) p = 0.16] compared with walking. Conclusions: E‐cycling was associated with increased physiological responses that can confer health benefits. [ABSTRACT FROM AUTHOR]

We investigated if calorie restriction (CR) preserved skeletal muscle oxidative capacity with aging after accounting for life span extension by CR, and determined if mitochondrial content, mitochondrial DNA integrity, and peroxisome proliferator-activated receptor gamma coactivator-1[alpha] (PGC-1[alpha]) were involved. Ad libitum-fed (AL) and CR animals representing young adult, late middle age, and senescence were studied. Whereas citrate synthase and complex IV activities were lower in plantaris and gastrocnemius muscle of young adult CR animals, in contrast to the 15%-40% decline in senescent AL animals, there was no decline with aging in CR animals. There was no decline in citrate synthase protein in gastrocnemius with aging in either group, suggesting that CR preserves oxidative capacity with aging by protecting mitochondrial function rather than content. This protection was independent of mitochondrial DNA damage between groups. However, there was a slower decline in PGC-1[alpha] gene expression with aging in CR versus AL animals, suggesting a better maintenance of mitochondrial biogenesis with aging in CR animals.

Different magnitudes and durations of postocchision reactive hyperemia were achieved by occluding different volumes of tissue with and without ischemic exercise to test the hypotheses that flow-mediated dilation (FMD) of the brachial artery would depend on the increase in peak flow rate or shear stress and that the position of the occlusion cuff would affect the response. The brachial artery FMD response was observed by high-frequency ultrasound imaging with curve fitting to minimize the effects of random measurement error in eight healthy, young, nonsmoking men. Reactive hyperemia was graded by 5-min occlusion distal to the measurement site at the wrist and the forearm and proximal to the site in the upper arm. Flow was further increased by exercise during occlusion at the wrist and forearm positions. For the two wrist occlusion conditions, flow increased eightfold and FMD was only 1 to 2% (P > 0.05). After the forearm and upper arm occlusions, blood flow was almost identical hut FMD after forearm occlusions was 3.4% (P < 0.05), whereas it was significantly greater (6.6%, P < 0.05) and more prolonged after proximal occlusion. Forearm occlusion plus exercise caused a greater and more prolonged increase in blood flow, yet FMD (7.0%) was qualitatively and quantitatively similar to that after proximal occlusion. Overall, the magnitude of FMD was significantly correlated with peak forearm blood flow (r = 0.59, P < 0.001), peak shear rate (r = 0.49, P < 0.002), and total 5-min reactive hyperemia (r = 0.52, P < 0.001). The prolonged FMD after upper arm occlusion suggests that the mechanism for FMD differs with occlusion cuff position. hyperemia; endothelium; shear stress; ischemic exercise; blood flow

There is increasing evidence that skeletal muscle microvascular (capillary) blood flow plays an important role in glucose metabolism by increasing the delivery of glucose and insulin to the myocytes. This process is impaired in insulin-resistant individuals. Studies suggest that in diet-induced insulin-resistant rodents, insulin-mediated skeletal muscle microvascular blood flow is impaired post-short-term high fat feeding, and this occurs before the development of myocyte or whole-body insulin resistance. These data suggest that impaired skeletal muscle microvascular blood flow is an early vascular step before the onset of insulin resistance. However, evidence of this is still lacking in humans. In this review, we summarise what is known about short-term high-calorie and/or high-fat feeding in humans. We also explore selected animal studies to identify potential mechanisms. We discuss future directions aimed at better understanding the 'early' vascular mechanisms that lead to insulin resistance as this will provide the opportunity for much earlier screening and timing of intervention to assist in preventing type 2 diabetes. [ABSTRACT FROM AUTHOR]

Insulin infusion increases skeletal muscle microvascular blood flow (MBF) in healthy people but is impaired during insulin resistance. However, we have shown that eliciting insulin secretion via oral glucose loading in healthy people impairs muscle MBF, whilst others have demonstrated intravenous glucose infusion stimulates MBF. We aimed to show that the route of glucose administration (oral versus intravenous) influences muscle MBF, and explore potential gut‐derived hormones that may explain these divergent responses. Ten healthy individuals underwent a 120 min oral glucose tolerance test (OGTT; 75 g glucose) and on a subsequent occasion an intravenous glucose tolerance test (IVGTT, bypassing the gut) matched for similar blood glucose excursions. Femoral artery and thigh muscle microvascular (contrast‐enhanced ultrasound) haemodynamics were measured at baseline and during the OGTT/IVGTT. Plasma insulin, C‐peptide, glucagon, non‐esterified fatty acids and a range of gut‐derived hormones and incretins (gastric inhibitory polypeptide (GIP) and glucagon‐like peptide‐1(GLP‐1)) were measured at baseline and throughout the OGTT/IVGTT. The IVGTT increased whereas the OGTT impaired MBF (1.3‐fold versus 0.5‐fold from baseline, respectively, P = 0.0006). The impairment in MBF during the OGTT occurred despite producing 2.8‐fold higher plasma insulin concentrations (P = 0.0001). The change in MBF from baseline (ΔMBF) negatively correlated with ΔGIP concentrations (r = −0.665, P < 0.0001). The natural log ratio of incretins GLP‐1:GIP was positively associated with ΔMBF (r = 0.658, P < 0.0001), suggesting they have opposing actions on the microvasculature. Postprandial hyperglycaemia per se does not acutely determine opposing microvascular responses between OGTT and IVGTT. Incretins may play a role in modulating skeletal muscle MBF in humans. Key points: Insulin or mixed nutrient meals stimulate skeletal muscle microvascular blood flow (MBF) to aid in the delivery of nutrients; however, this vascular effect is lost during insulin resistance.Food/drinks containing large glucose loads impair MBF in healthy people; however, this impairment is not observed when glucose is infused intravenously (bypassing the gut).We investigated skeletal muscle MBF responses to a 75 g oral glucose tolerance test and intravenous glucose infusion and aimed to identify potential gut hormones responsible for glucose‐mediated changes in MBF.Despite similar blood glucose concentrations, orally ingested glucose impaired, whereas intravenously infused glucose augmented, skeletal muscle MBF. The incretin gastric inhibitory polypeptide was negatively associated with MBF, suggestive of an incretin‐mediated MBF response to oral glucose ingestion.This work provides new insight into why diets high in glucose may be detrimental to vascular health and provides new avenues for novel treatment strategies targeting microvascular dysfunction. [ABSTRACT FROM AUTHOR]

Supplemental digital content is available in the text. Purpose: Whole-body vibration (WBV) therapy has been reported to potentially act as an exercise mimetic by improving muscle function and exercise capacity in a variety of healthy and clinical populations. Considering the important role that microvascular blood flow plays in muscle metabolism and exercise capacity, we investigated the muscle microvascular responses of acute WBV to knee extension exercise (KEX) in healthy individuals. Methods: Eleven healthy adults (age: 33 ± 2 yr; body mass index: 23.6 ± 1.1 kg·m−2) underwent 3 min of WBV, or 3 min of KEX at 25% of one-repetition maximum, in a randomized order separated by a minimum of 72 h. Femoral arterial blood flow was measured via Doppler ultrasound, and thigh muscle microvascular blood flow was measured via contrast-enhanced ultrasound at baseline and throughout the 3-min postintervention recovery period. Results: Both WBV and KEX significantly increased peak microvascular blood flow (WBV, 5.6-fold; KEX, 21-fold; both P < 0.05) during the 3-min recovery period. Despite a similar increase in femoral arterial blood flow (~4-fold; both P < 0.05 vs baseline) and whole-body oxygen consumption measured by indirect calorimetry (WBV, 48%; KEX, 60%; both P < 0.05 vs baseline) in both conditions, microvascular blood flow was stimulated to a greater extent after KEX. Conclusion: A single 3-min session of WBV in healthy individuals is sufficient to significantly enhance muscle microvascular blood flow. Despite KEX providing a more potent stimulus, WBV may be an effective method for improving microvascular blood flow in populations reported to exhibit microvascular dysfunction such as patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Key points: Exercise, insulin‐infusion and low‐glucose mixed‐nutrient meal ingestion increases muscle microvascular blood flow which in part facilitates glucose delivery and disposal. In contrast, high‐glucose ingestion impairs muscle microvascular blood flow which may contribute to impaired postprandial metabolism.We investigated the effects of prior cycling exercise on postprandial muscle microvascular blood flow responses to a high‐glucose mixed‐nutrient meal ingested 3 and 24 h post‐exercise.Prior exercise enhanced muscle microvascular blood flow and mitigated microvascular impairments induced by a high‐glucose mixed meal ingested 3 h post‐exercise, and to a lesser extent 24 h post‐exercise.High‐glucose ingestion 3 h post‐exercise leads to greater postprandial blood glucose, non‐esterified fatty acids, and fat oxidation, and a delay in the insulin response to the meal compared to control.Effects of acute exercise on muscle microvascular blood flow persist well after the cessation of exercise which may be beneficial for conditions characterized by microvascular and glycaemic dysfunction. Exercise, insulin‐infusion and low‐glucose mixed‐nutrient meal ingestion lead to increased muscle microvascular blood flow (MBF), whereas high‐glucose ingestion impairs MBF. We investigated whether prior cycling exercise could enhance postprandial muscle MBF and prevent MBF impairments induced by high‐glucose mixed‐nutrient meal ingestion. In a randomized cross‐over design, eight healthy young men ingested a high‐glucose mixed‐nutrient meal (1.1 g glucose/kg body weight; 45% carbohydrate, 20% protein and 35% fat) after an overnight fast (no‐exercise control) and 3 h and 24 h after moderate‐intensity cycling exercise (1 h at 70–75% V̇O2peak). Skeletal muscle MBF, measured directly by contrast‐enhanced ultrasound, was lower at 60 min and 120 min postprandially compared to baseline in all conditions (P < 0.05), with a greater decrease occurring from 60 min to 120 min in the control (no‐exercise) condition only (P < 0.001). Despite this meal‐induced decrease, MBF was still markedly higher compared to control in the 3 h post‐exercise condition at 0 min (pre‐meal; 74%, P = 0.004), 60 min (112%, P = 0.002) and 120 min (223%, P < 0.001), and in the 24 h post‐exercise condition at 120 min postprandially (132%, P < 0.001). We also report that in the 3 h post‐exercise condition postprandial blood glucose, non‐esterified fatty acids (NEFAs), and fat oxidation were substantially elevated, and the insulin response to the meal delayed compared to control. This probably reflects a combination of increased post‐exercise exogenous glucose appearance, substrate competition, and NEFA‐induced insulin resistance. We conclude that prior cycling exercise elicits long‐lasting effects on muscle MBF and partially mitigates MBF impairments induced by high‐glucose mixed‐nutrient meal ingestion. Key points: Exercise, insulin‐infusion and low‐glucose mixed‐nutrient meal ingestion increases muscle microvascular blood flow which in part facilitates glucose delivery and disposal. In contrast, high‐glucose ingestion impairs muscle microvascular blood flow which may contribute to impaired postprandial metabolism.We investigated the effects of prior cycling exercise on postprandial muscle microvascular blood flow responses to a high‐glucose mixed‐nutrient meal ingested 3 and 24 h post‐exercise.Prior exercise enhanced muscle microvascular blood flow and mitigated microvascular impairments induced by a high‐glucose mixed meal ingested 3 h post‐exercise, and to a lesser extent 24 h post‐exercise.High‐glucose ingestion 3 h post‐exercise leads to greater postprandial blood glucose, non‐esterified fatty acids, and fat oxidation, and a delay in the insulin response to the meal compared to control.Effects of acute exercise on muscle microvascular blood flow persist well after the cessation of exercise which may be beneficial for conditions characterized by microvascular and glycaemic dysfunction. [ABSTRACT FROM AUTHOR]

Androgen deprivation therapy (ADT) decreases muscle mass, force, and physical activity levels, but it is unclear whether disuse atrophy and testosterone suppression are additive. Additionally, conflicting reports exist on load-mediated hypertrophy during ADT and if protein supplementation offsets these deficits. This study sought to determine the role of testosterone suppression and a high-protein diet on 1) immobilization-induced atrophy and 2) muscle regrowth during reloading. Eight-week-old male Fischer 344 rats underwent sham surgery (Sham), castration surgery (ORX), or ORX and a high-casein diet supplemented with branched-chain amino acids (BCAA) (ORXCAS/AA) followed by 10 days of unilateral immobilization (IMM) and 0, 6, or 14 days of reloading. With IMM, body mass gains were ~8% greater than ORX and ORXCAS/AA that increased to 15% during reloading (both P < 0.01). IMM reduced muscle mass by 11-34% (all P < 0.01) and extensor digitorum longus and soleus (SOL) force by 21% and 49% (both P < 0.01), respectively, with no group differences. During reloading, castration reduced gastrocnemius mass (~12%) at 6 days and SOL mass (~20%) and SOL force recovery (~46%) at 14 days relative to Sham (all P < 0.05). Specific force reduced castration deficits, indicating that muscle atrophy was a key contributor. IMM decreased SOL cross-sectional area by 30.3% (P < 0.001), with a trend for reduced regrowth in ORX and ORXCAS/AA following reloading (P < 0.083). Castration did not exacerbate disuse atrophy but may impair recovery of muscle function, with no benefit from a CAS/AA diet during reloading. Examining functional outcomes in addition to muscle mass during dietary interventions provides novel insights into muscle regrowth during ADT. NEW & NOTEWORTHY Low testosterone levels during skeletal muscle disuse did not worsen declines in muscle mass and function, although hypogonadism may attenuate recovery during subsequent reloading. Diets high in casein did not improve outcomes during immobilization or reloading. Practical strategies are needed that do not compromise caloric intake yet provide effective protein doses to augment these adverse effects. [ABSTRACT FROM AUTHOR]

Oral glucose ingestion leads to impaired muscle microvascular blood flow (MBF), which may contribute to acute hyperglycemia-induced insulin resistance. We investigated whether incorporating lipids and protein into a high-glucose load would prevent postprandial MBF dysfunction. Ten healthy young men (age, 27 yr [24, 30], mean with lower and upper bounds of the 95% confidence interval; height, 180 cm [174, 185]; weight, 77 kg [70, 84]) ingested a high-glucose (1.1 g/kg glucose) mixed-nutrient meal (10 kcal/kg; 45% carbohydrate, 20% protein, and 35% fat) in the morning after an overnight fast. Femoral arterial blood flow was measured via Doppler ultrasound, and thigh MBF was measured via contrast-enhanced ultrasound, before meal ingestion and 1 h and 2 h postprandially. Blood glucose and plasma insulin were measured at baseline and every 15 min throughout the 2-h postprandial period. Compared with baseline, thigh muscle microvascular blood volume, velocity, and flow were significantly impaired at 60 min postprandial (25%, 27%, and 46%, respectively; all P < 0.05) and to a greater extent at 120 min postprandial (37%, 46%, and 64%; all P < 0.01). Heart rate and femoral arterial diameter, blood velocity, and blood flow were significantly increased at 60 min and 120 min postprandial (all P < 0.05). Higher blood glucose area under the curve was correlated with greater MBF dysfunction (R2 = 0.742; P < 0.001). Ingestion of a high-glucose mixed-nutrient meal impairs MBF in healthy individuals for up to 2 h postprandial. [ABSTRACT FROM AUTHOR]

Skeletal muscle contributes to ~40% of total body mass and has numerous important mechanical and metabolic roles in the body. Skeletal muscle is a major site for glucose disposal following a meal. Consequently, skeletal muscle plays an important role in postprandial blood glucose homeostasis. Over the past number of decades, research has demonstrated that insulin has an important role in vasodilating the vasculature in skeletal muscle in response to an insulin infusion (hyperinsulinaemic‐euglycaemic clamp) or following the ingestion of a meal. This vascular action of insulin is pivotal for glucose disposal in skeletal muscle, as insulin‐stimulated vasodilation increases the delivery of both glucose and insulin to the myocyte. Notably, in insulin‐resistant states such as obesity and type 2 diabetes, this vascular response of insulin in skeletal muscle is significantly impaired. Whereas the majority of work in this field has focussed on the action of insulin alone on skeletal muscle microvascular blood flow and myocyte glucose metabolism, there is less understanding of how the consumption of a meal may affect skeletal muscle blood flow. This is in part due to complex variations in glucose and insulin dynamics that occurs postprandially—with changes in humoral concentrations of glucose, insulin, amino acids, gut and pancreatic peptides—compared to the hyperinsulinaemic‐euglycaemic clamp. This review will address the emerging body of evidence to suggest that postprandial blood flow responses in skeletal muscle may be a function of the nutritional composition of a meal. [ABSTRACT FROM AUTHOR]

We investigated the effects of testosterone suppression, hindlimb immobilization, and recovery on skeletal muscle Na+,K+-ATPase (NKA), measured via [3H]ouabain binding site content (OB) and NKA isoform abundances (α1-3, &#946L1-2). Male rats underwent castration or sham surgery plus 7 days of rest, 10 days of unilateral immobilization (cast), and 14 days of recovery, with soleus muscles obtained at each time from cast and noncast legs. Testosterone reduction did not modify OB or NKA isoforms in nonimmobilized control muscles. With sham surgery, OB was lower after immobilization in the cast leg than in both the noncast leg (26%, P = 0.023) and the nonimmobilized control (34%, P = 0.001), but OB subsequently recovered. With castration, OB was lower after immobilization in the cast leg than in the nonimmobilized control (34%, P = 0.001), and remained depressed at recovery (34%, P = 0.001). NKA isoforms did not differ after immobilization or recovery in the sham group. After castration, α2 in the cast leg was ~60% lower than in the noncast leg (P = 0.004) and nonimmobilized control (P - 0.004) and after recovery remained lower than the nonimmobilized control (-42%, P = 0.039). After immobilization, α1 was lower in the cast than the noncast leg (26%, P = 0.018), with β2 lower in the cast leg than in the noncast leg (71%, P = 0.004) and nonimmobilized control (65%, P = 0.012). No differences existed for α1 or α3. Thus, both OB and α2 decreased after immobilization and recovery in the castration group, with α2, β1, and β2 isoform abundances decreased with immobilization compared with the sham group. Therefore, testosterone suppression in rats impaired restoration of immobilization-induced lowered number of functional NKA and α2 isoforms in soleus muscle. [ABSTRACT FROM AUTHOR]

This study was designed to examine the biomechanical and physiological responses between cycling on the Axiom stationary ergometer (Axiom, Elite, Fontaniva, Italy) vs. field conditions for both uphill and level ground cycling. Nine cyclists performed cycling bouts in the laboratory on an Axiom stationary ergometer and on their personal road bikes in actual road cycling conditions in the field with three pedaling cadences during uphill and level cycling. Gross efficiency and cycling economy were lower (-10%) for the Axiom stationary ergometer compared with the field. The preferred pedaling cadence was higher for the Axiom stationary ergometer conditions compared with the field conditions only for uphill cycling. Our data suggests that simulated cycling using the Axiom stationary ergometer differs from actual cycling in the field. These results should be taken into account notably for improving the precision of the model of cycling performance, and when it is necessary to compare two cycling test conditions (field/laboratory, using different ergometers). [ABSTRACT FROM AUTHOR]

Insulin stimulates glucose disposal in skeletal muscle in part by increasing microvascular blood flow, and this effect is blunted during insulin resistance. We aimed to determine whether metformin treatment improves insulin-mediated glucose disposal and vascular insulin responsiveness in skeletal muscle of insulin-resistant rats. Sprague--Dawley rats were fed a normal (ND) or high-fat (HFD) diet for 4 weeks. A separate HFD group was given metformin in drinking water (HFD + MF, 150 mg/kg/day) dur ing the final 2 weeks. After the intervention, overnight-fasted (food and metformin removed) anaesthetised rats underwent a 2-h euglycaemic--hyperinsulinaemic clamp (10 mU/min/kg) or saline infusion. Femoral artery blood flow, hindleg muscle microvascula r blood flow, muscle glucose disposal and muscle signalling (Ser473-AKT and Thr172-AMPK phosphorylation) were measured. HFD rats had elevated body weight, epididymal fat pad weight, fasting plasma insulin and free fatty acid levels when compared to ND. HFD-fed animals displayed whole-body and skeletal muscle insulin resistance and blunting of insulinstimulated femoral artery blood flow, muscle microvascular blood flow and skeletal muscle insulin-stimulated Ser473-AKT phosphorylation. Metformin treatment of HFD rats reduced fasting insulin and free fatty acid concentrations and lowered body weight and adiposity. During euglycaemic-hyperinsulinaemic clamp, metformin-treated animals showed improved vascular responsiveness to insulin, improved insulin-stimulated muscle Ser473-AKT phosphorylation but only partially restored (60%) muscle glucose uptake. This occurred without any detectable levels of metformin in plasma or change in muscle Thr172-AMPK phosphorylation. We conclude that 2-week metformin treatm ent is effective at improving vascular and metabolic insulin responsive ness in muscle of HFDinduced insulin-resistant rats. [ABSTRACT FROM AUTHOR]

Skeletal muscle contraction increases glucose uptake via an insulin-independent mechanism. Signaling pathways arising from mechanical strain are activated during muscle contractions, and mechanical strain in the form of passive stretching stimulates glucose uptake. However, the exact mechanisms regulating stretch-stimulated glucose uptake are not known. Since nitric oxide synthase (NOS) has been implicated in the regulation of glucose uptake during ex vivo and in situ muscle contractions and during exercise, and NO is increased with stretch, we examined whether the increase in muscle glucose uptake during stretching involves NOS. We passively stretched isolated extensor digitorum longus muscles (15 min at ~100–130 mN) from control mice and mice lacking either neuronal NOSµ (nNOSµ) or endothelial NOS (eNOS) isoforms, as well as used pharmacological inhibitors of NOS. Stretch significantly increased muscle glucose uptake appoximately twofold (P < 0.05), and this was unaffected by the presence of the NOS inhibitors NG-monomethyl-l-arginine (100 µM) or NG-nitro-l-arginine methyl ester (100 µM). Similarly, stretch-stimulated glucose uptake was not attenuated by deletion of either eNOS or nNOSµ isoforms. Furthermore, stretching failed to increase skeletal muscle NOS enzymatic activity above resting levels. These data clearly demonstrate that stretch-stimulated skeletal muscle glucose uptake is not dependent on NOS. NEW & NOTEWORTHY Passive stretching is known to activate muscle glucose uptake through mechanisms that partially overlap with contraction. We report that genetic knockout of endothelial nitric oxide synthase (NOS) or neuronal NOS or pharmacological NOS inhibition does not affect stretch-stimulated glucose uptake. Passive stretch failed to increase NOS activity above resting levels. This information is important for the study of signaling pathways that regulate stretch-stimulated glucose uptake and indicate that NOS should be excluded as a potential signaling factor in this regard. [ABSTRACT FROM AUTHOR]

Insulin resistance is a major health risk, and although exercise clearly improves skeletal muscle insulin sensitivity, the mechanisms are unclear. Here we show that initiation of a euglycemic-hyperinsulinemic clamp 4 h after single-legged exercise in humans increased microvascular perfusion (determined by contrast-enhanced ultrasound) by 65% in the exercised leg and 25% in the rested leg (P < 0.05) and that leg glucose uptake increased 50% more (P < 0.05) in the exercised leg than in the rested leg. Importantly, infusion of the nitric oxide synthase inhibitor l-NG-monomethyl-l-arginine acetate (l-NMMA) into both femoral arteries reversed the insulin-stimulated increase in microvascular perfusion in both legs and abrogated the greater glucose uptake in the exercised compared with the rested leg. Skeletal muscle phosphorylation of TBC1D4 Ser318 and Ser704 and glycogen synthase activity were greater in the exercised leg before insulin and increased similarly in both legs during the clamp, and l-NMMA had no effect on these insulin-stimulated signaling pathways. Therefore, acute exercise increases insulin sensitivity of muscle by a coordinated increase in insulin-stimulated microvascular perfusion and molecular signaling at the level of TBC1D4 and glycogen synthase in muscle. This secures improved glucose delivery on the one hand and increased ability to take up and dispose of the delivered glucose on the other hand. [ABSTRACT FROM AUTHOR]

ABSTRACT Undercarboxylated osteocalcin (ucOC) has been implicated in skeletal muscle insulin sensitivity and function. However, whether muscle mass and strength loss in atrophic conditions is related to a reduction in ucOC is not clear. We hypothesized that both immobilization and testosterone depletion would lead to reductions in ucOC, associated with not only the degree of muscle atrophy but also changes to atrophy signaling pathway(s) in male rats. We subjected 8-week-old male Fischer (F344) rats to 7 days of hindlimb immobilization 10 days after castration surgery. Hindlimb immobilization, but not castration, resulted in a significant reduction in ucOC (30%) and lower ucOC was correlated with the degree of muscle loss and muscle weakness. ucOC levels, the expression of ucOC-sensitive receptor G protein-coupled receptor, class C, group 6, member A (GPRC6A), as well as the activity of extracellular signal-regulated kinase (ERK) and 5′ adenosine monophosphate-activated protein kinase (AMPK) were associated with the expression and activity of a number of proteins in the mammalian target of rapamycin complex 1 (mTORC1) and Forkhead Box O (FOXO) signaling pathways in a muscle type-specific manner. These data suggest that ucOC may have other effects on skeletal muscle in addition to its insulin sensitizing effect. © 2016 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Nitric oxide influences intramuscular signaling that affects skeletal muscle glucose uptake during exercise. The role of the main NO-producing enzyme isoform activated during skeletal muscle contraction, neuronal nitric oxide synthase- μ (nNOSμ), in modulating glucose uptake has not been investigated in a physiological exercise model. In this study, conscious and unrestrained chronically catheterized nNOSμ+/+ and nNOSμ-/- mice either remained at rest or ran on a treadmill at 17 m/min for 30 min. Both groups of mice demonstrated similar exercise capacity during a maximal exercise test to exhaustion (17.7 ± 0.6 vs. 15.9 ± 0.9 min for nNOSμ+/+ and nNOSμ-/-, respectively, P > 0.05). Resting and exercise blood glucose levels were comparable between the genotypes. Very low levels of NOS activity were detected in skeletal muscle from nNOSμ-/- mice, and exercise increased NOS activity only in nNOSμ+/+ mice (4.4 ± 0.3 to 5.2 ± 0.4 pmol·mg-1·min-1, P · 0.05). Exercise significantly increased glucose uptake in gastrocnemius muscle (5- to 7-fold) and, surprisingly, more so in nNOSμ-/- than in nNOSμ+/+ mice (P < 0.05). This is in parallel with a greater increase in AMPK phosphorylation during exercise in nNOSμ-/- mice. In conclusion, nNOSμ is not essential for skeletal muscle glucose uptake during exercise, and the higher skeletal muscle glucose uptake during exercise in nNOSμ-/- mice may be due to compensatory increases in AMPK activation. [ABSTRACT FROM AUTHOR]

Background and Aims: Obesity and impairments in metabolic health are associated with reductions in exercise capacity. Both whey protein isolates (WPIs) and vitamin E tocotrienols (TCTs) exert favorable effects on obesity-related metabolic parameters. This research sought to determine whether these supplements improved exercise capacity and increased glucose tolerance in diet-induced obese rats. Methods: Six week old male rats (n = 35) weighing 187 ± 32g were allocated to either: Control (n = 9), TCT (n = 9), WPI (n = 8) or TCT + WPI (n = 9) and placed on a high-fat diet (40% of energy from fat) for 10 weeks. Animals received 50mg/kg body weight and 8% of total energy intake per day of TCTs and/or WPIs respectively. Food intake, body composition, glucose tolerance, insulin sensitivity, exercise capacity, skeletal muscle glycogen content and oxidative enzyme activity were determined. Results: Both TCT and WPI groups ran >50% longer (2271 ± 185m and 2195 ± 265m respectively) than the Control group (1428 ± 139m) during the run to exhaustion test (P<0.05), TCT + WPI did not further improve exercise endurance (2068 ± 104m). WPIs increased the maximum in vitro activity of beta-hydroxyacyl-CoA in the soleus muscle (P<0.05 vs. Control) but not in the plantaris. Citrate synthase activity was not different between groups. Neither supplement had any effect on weight gain, adiposity, glucose tolerance or insulin sensitivity. Conclusion: Ten weeks of both TCTs and WPIs increased exercise endurance by 50% in sedentary, diet-induced obese rats. These positive effects of TCTs and WPIs were independent of body weight, adiposity or glucose tolerance. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) has been shown to be involved in skeletal muscle glucose uptake during contraction/ exercise, especially in individuals with Type 2 diabetes (T2D). To examine the potential mechanisms, we examined the effect of local NO synthase (NOS) inhibition on muscle glucose uptake and muscle capillary blood flow during contraction in healthy and T2D rats. T2D was induced in Sprague-Dawley rats using a combined high-fat diet (23% fat wt/wt for 4 wk) and low-dose streptozotocin injections (35 mg/kg). Anesthetized animals had one hindlimb stimulated to contract in situ for 30 min (2 Hz, 0.1 ms, 35 V) with the contralateral hindlimb rested. After 10 min, the NOS inhibitor, W-nitro-L-arginine methyl ester (L-NAME; 5 μM) or saline was continuously infused into the femoral artery of the contracting hindlimb until the end of contraction. Surprisingly, there was no increase in skeletal muscle NOS activity during contraction in either group. Local NOS inhibition had no effect on systemic blood pressure or muscle contraction force, but it did cause a significant attenuation of the increase in femoral artery blood flow in control and T2D rats. However, NOS inhibition did not attenuate the increase in muscle capillary recruitment during contraction in these rats. Muscle glucose uptake during contraction was significantly higher in T2D rats compared with controls but, unlike our previous findings in hooded Wistar rats, NOS inhibition had no effect on glucose uptake during contraction. In conclusion, NOS inhibition did not affect muscle glucose uptake during contraction in control or T2D Sprague-Dawley rats, and this may have been because there was no increase in NOS activity during contraction. [ABSTRACT FROM AUTHOR]

Inhibition of nitric oxide synthase (NOS) significantly attenuates the increase in skeletal muscle glucose uptake during contraction/exercise, and a greater attenuation is observed in individuals with Type 2 diabetes compared with healthy individuals. Therefore, NO appears to play an important role in mediating muscle glucose uptake during contraction. In this study, we investigated the involvement of neuronal NOSµ (nNOSµ), the main NOS isoform activated during contraction, on skeletal muscle glucose uptake during ex vivo contraction. Extensor digitorum longus muscles were isolated from nNOSµ and nNOSµ+/+ mice. Muscles were contracted ex vivo in a temperature-controlled (30°C) organ bath with or without the presence of the NOS inhibitor NG-monomethyl-L-arginine (L-NMMA) and the NOS substrate L-arginine. Glucose uptake was determined by radioactive tracers. Skeletal muscle glucose uptake increased approximately fourfold during contraction in muscles from both nNOSµ-/- and nNOSµ+/+ mice. L-NMMA significantly attenuated the increase in muscle glucose uptake during contraction in both genotypes. This attenuation was reversed by L-arginine, suggesting that L-NMMA attenuated the increase in muscle glucose uptake during contraction by inhibiting NOS and not via a nonspecific effect of the inhibitor. Low levels of NOS activity (~4%) were detected in muscles from nNOSµ-/- mice, and there was no evidence of compensation from other NOS isoform or AMP-activated protein kinase which is also involved in mediating muscle glucose uptake during contraction. These results indicate that NO regulates skeletal muscle glucose uptake during ex vivo contraction independently of nNOSµ. [ABSTRACT FROM AUTHOR]

Aging skeletal muscle shows an increased time to peak force and relaxation and a decreased specific force, all of which could relate to changes in muscle Ca2+ handling. The purpose of this study was to determine if Ca2+-handling protein content and function are decreased in senescent gastrocnemius muscle and if initiating a training program in late middle age (LMA, 29 mo old) could improve function in senescent (34to 36-mo-old) muscle. LMA male Fischer 344 × Brown-Norway rats underwent 5-7 mo of treadmill training. Aging resulted in a decrease in maximal sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) activity and a decrease in Ca2+ release rate but no change in Ca2+ uptake rate. Efficiency of the Ca2+ pump was increased with age, as was the content of SERCA2a. Training caused a further increase in SERCA2a content. Aging also caused an increase in protein carbonyl and reactive nitrogen species damage accumulation, and both further increased with training. Consistent with the increase in oxidative damage, heat shock protein 70 content was increased with age and further increased with training. Together, these results suggest that while initiating exercise training in LMA augments the age-related increase in expression of heat shock protein 70 and the more efficient SERCA2a isoform, it did not prevent the decrease in SERCA activity and exacerbated oxidative damage in senescent gastrocnemius muscle. [ABSTRACT FROM AUTHOR]

Aging is associated with a progressive decline in the capacity for physical activity. Central to this decline is a reduction in the maximal rate of oxygen utilization, or VO2 max. This critical perspective examines the roles played by the factors that determine the rate of muscle oxygen delivery versus those that determine the utilization of oxygen by muscle as a means of probing the reasons for VO2 max decline with aging. Reductions in muscle oxygen delivery, principally due to reduced cardiac output and perhaps also a maldistribution of cardiac output, appear to play the dominant role up until late middle age. On the other hand, there is a decline in skeletal muscle oxidative capacity with aging, due in part to mitochondrial dysfunction, which appears to play a particularly important role in extreme old age (senescence) where skeletal muscle VO2 max is observed to decline by approximately 50% even under conditions of similar oxygen delivery as young adult muscle. It is noteworthy that at least the structural aspects of the capillary bed do not appear to be reduced in a manner that would compromise the capacity for muscle oxygen diffusion even in senescence. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to measure the electromyographic (EMG) activity of four lower limb muscles and the propulsive torque during a cycling time-trial (TT). Nine competitive cyclists (VO2max: 73.8 ± 5.3 ml·min-1·kg-1) performed two tests separated over a one-week period on a friction-load cycle ergometer equipped with a SRM crankset scientific system: 1) a continuous incremental test for the determination of the peak power output (PPO): and 2) a 30-min TT test at a self-selected work intensity. The EMG activity of the vastus medialis (VM), the rectus femoris (RF), the biceps femoris (HF), and the gastrocnemius medialis (GAS), and the propulsive torque were recorded every 5 min for 10s. There was no time effect on the power output, the pedalling cadence, and the mean propulsive torque. The EMG activity of the VM and the RF muscles was unchanged during the IT (p >0.05). The EMG activity of the two knee flexor muscles (BF and GAS) tended to increase with time but it was not significant (p > 0.05). The EMG/torque of the VM and the RF muscles tended to decrease with time but it was not significant (p > 0.05). The lack of increase in the EMG activity of the tour investigated muscles seems to indicate that the subjects performed the TT test at a muscular work steady-state. [ABSTRACT FROM AUTHOR]

STUDY DESIGN:: Before and after investigation of the effects of a wheelchair ergometer Training programme. OBJECTIVE:: To investigate the effects of an original interval-training programme on work capacity and cardiorespiratory variables with spinal cord-injured persons (SCIP's) on a wheelchair-specific ergometer. SETTING:: BESANCON, FRANCE. METHODS:: Seven SCIP's (male) performed 45?min of wheelchair ergometry three times per week, for 6 weeks. Training effects on maximal dynamic performance and endurance capacity were studied by comparison of performance and cardiorespiratory responses observed during both a maximal progressive test (10?W/2?min) and the same training session performed before and after training. RESULTS:: Training induced significant improvements in maximal tolerated power (+19.6%), in peak oxygen consumption (VO2+16%), and in oxygen pulse (O2p,+18.7%).At ventilatory threshold, significant improvements were also observed in power output (+63%), VO2VT(+ 34.1), ventilation VEVT(+ 37.1%), and V2pVT(+ 19.9% ). Heart rate and ventilation were significantly lower (-11 and -14.6%, respectively) after training at the same work rate, while VO2 was unchanged. Between the first and the last training session, the total physical work was improved by 24.7%, whereas heart rate was unchanged. CONCLUSION:: An interval-training programme individualised to each paraplegic subject using a wheelchair ergometer can significantly improve the fitness level and endurance capacity.Spinal Cord (2003) 41, 451-456. doi:10.1038/sj.sc.3101475 [ABSTRACT FROM AUTHOR]

Microvascular blood flow (MBF) enables the delivery of key nutrients (e.g., lipids and glucose) and hormones (e.g., insulin) to adipose tissue. We have demonstrated that adipose tissue MBF is impaired in people with type 2 diabetes (T2D), postprandially. Whether this also occurs in people at risk of T2D (having a family history of T2D) is unknown. Eighteen healthy people with no family history of T2D for two generations (FH-), and sixteen healthy people with at least one parent with T2D (FH+) were recruited. Overnight-fasted participants had a blood sample taken for clinical chemistries, a DEXA scan performed for body composition and underwent a mixed meal challenge (MMC, 300kCal; 54% carbohydrate, 29% protein and 16% fat). Microvascular blood volume (MBV), velocity (β) and MBF in truncal subcutaneous adipose tissue was assessed by contrast-enhanced ultrasound before and 60 min post-MMC. Both groups were matched for age, BMI, clinical chemistries and post-MMC area under the glucose time curve (Table 1). FH+ had higher truncal fat (Table 1). Increases in adipose tissue MBF post-MMC were lower in FH+ which was mostly attributed to a lower MBV (Table 1). Despite having normal clinical chemistries and blood glucose regulation, FH+ have impaired post-prandial adipose tissue MBF coinciding with greater central obesity which might in part explain their heightened risk for developing T2D. Disclosure: K. Roberts-Thomson: None. R.D. Russell: None. D. Hu: None. T.M. Greenaway: Advisory Panel; Self; Eli Lilly and Company. Speaker's Bureau; Self; AstraZeneca, Sanofi-Aventis. A.C. Betik: None. L. Parker: None. S.M. Richards: None. D. Premilovac: None. M. Keske: None. [ABSTRACT FROM AUTHOR]

Skeletal muscle microvascular blood flow (MBF) increases in response to an insulin infusion (hyperinsulinemic-euglycemic clamp) or the consumption of a mixed meal to augment glucose disposal. This microvascular action is impaired during insulin resistance. We recently demonstrated that an oral glucose challenge (50g glucose) acutely impairs skeletal muscle MBF in healthy people, compared to a mixed meal challenge, despite similar levels of hyperinsulinemia. We aimed to determine whether post-prandial hyperglycemia or gut-derived factors are the primary mediators of impaired MBF observed in response to orally ingested glucose. Seven healthy overnight-fasted subjects (sex 2M/5F, age 29±9 yrs, BMI 23.5±3.2 kg/m2, blood glucose 4.5±0.3 mM, HbA1c 5.2±0.3%, total cholesterol 3.9±1.0 mM, triglycerides 0.8±0.3 mM) underwent an oral glucose tolerance test (OGTT, 75g glucose) and an intravenous glucose tolerance test (IVGTT- bypassing the gut) matched for similar blood glucose levels, on successive visits (<4 weeks apart: cross-over design). MBF was assessed in the vastus lateralis by contrast-enhanced ultrasound at baseline, 60 and 120 minutes post-OGTT and -IVGTT. Despite similar area under the glucose time curve (OGTT: 846.8±124.8, IVGTT: 845.9±121.1 mMx2hr, P=0.98), MBF was only stimulated with the IVGTT, at 60 min (Δ MBF: OGTT -0.3± 0.5; IVGTT 0.3± 0.3 Acoustic intensity/sec, P=0.02) and 120 min post- infusion (Δ MBF: OGTT -0.4± 0.3; IVGTT 0.2± 0.3 Acoustic intensity/sec, P<0.01). Therefore, the extent of post-prandial hyperglycemia per se does not acutely impact microvascular responses in skeletal muscle in healthy humans. These data support the role of gut-derived factor(s) in the impairment of MBF following orally ingested glucose. These findings have important physiological implications for the consumption of high glycemic index meals. Disclosure: K. Roberts-Thomson: None. L. Parker: None. A.C. Betik: None. M. Keske: None. [ABSTRACT FROM AUTHOR]

Skeletal muscle microvascular blood volume increases after a meal to increase glucose and insulin delivery to the muscle. In obese individuals this microvascular action in muscle is lost (Keske et al. 2009 Diabetes Care). However, exercise training can improve muscle microvascular responses in the postprandial state (Russell et al. 2017 Diabetes Care). We hypothesized that people who are overweight but are habitual exercisers would have similar increases in microvascular perfusion following a mixed meal as people who are lean and exercise regularly. Methods: Nine lean (LEAN+Ex, BMI < 23 kg/m2) and five overweight (OW+Ex, BMI > 27 kg/m2) physically active participants (> 75 min of vigorous intensity or > 150 min of moderate intensity exercise per week) were recruited. Body composition was assessed by DEXA. After an overnight fast, participants underwent a mixed meal challenge (1214 kJ). Thigh muscle microvascular responses were assessed by contrast-enhanced ultrasound at rest and 1 hour after the mixed meal. Results: Data are presented in Table 1 (Mean ± SE, * p<0.05 vs. LEAN+Ex; + p<0.05 vs. resting). Conclusion: The postprandial increase in microvascular blood volume in the Lean+Ex group was not observed in the OW+Ex group. These data suggest that habitual exercise is not sufficient to overcome the negative effects of being overweight on muscle microvascular responses to a mixed meal. Disclosure: A.C. Betik: None. D.J. Morrison: None. L. Parker: None. K. Roberts-Thomson: None. M. Keske: None. Funding: Institute for Physical Activity and Nutrition [ABSTRACT FROM AUTHOR]