Collagen peptide supplementation for pain and function: is it effective?

PURPOSE OF REVIEW: Connective tissue injuries are prevalent in active and aging populations, leading to chronic pain and decreased function. Turnover of this tissue is not well understood, especially as it relates to aging and injury. Supplementation of collagen peptides has been shown to improve connective tissue recovery and pain through increased collagen production. RECENT FINDINGS: Collagen peptide supplementation improves pain and function, and upregulates metabolic pathways associated with muscle and tendon growth. Literature from the past 12-18 months supports that these pathways are also involved with increased synthesis and degradation of collagen and other elements of the extracellular matrix. Improvements in body composition and strength have been noted with collagen peptide supplementation when paired with resistance training. Collagen peptide supplements are hydrolyzed into small peptides, termed bioactive peptides, and individual amino acids. These bioactive peptides are associated with the benefits observed with collagen peptide supplementation and may play a critical role in the collagen turnover. SUMMARY: Collagen peptide supplementation has been shown to promote recovery, decrease pain, and improve strength and body composition when paired with resistance training. These benefits may be attributed to bioactive peptides in collagen peptide supplements. Additional research is warranted to examine the specific effects of these bioactive peptides.

Lipolysis and Fat Oxidation Are Not Altered with Presleep Compared with Daytime Casein Protein Intake in Resistance-Trained Women.

BACKGROUND: To date, no studies have directly compared the differences between presleep and daytime protein (PRO) consumption on localized and systemic fat metabolism in active women. OBJECTIVE: The purpose of this study was to assess the effects of presleep compared with daytime PRO supplementation on subcutaneous abdominal adipose tissue (SCAAT) lipolysis and whole-body substrate utilization in women. METHODS: Thirteen young (mean ± SE age: 22 ± 1 y; BMI: 24.3 ± 0.8 kg/m2), resistance-trained [1 repetition maximum (1RM) squat percentage of body weight: 135% ± 6%; 1RM bench press percentage of body weight: 82% ± 4%] women volunteered. On overnight experimental visits, participants performed full-body resistance exercise (RE; 65% 1RM) and were randomly assigned to consume either daytime PRO (PRO, 30 g casein) 30 min post-RE and presleep (30 min before bed) noncaloric, sensory-matched placebo (PLA, 0 g casein) (PRO-PLA), or the opposite (PLA-PRO), switching the order of the supplements on the following visit. SCAAT lipolysis, resting metabolism (indirect calorimetry), and plasma biomarkers (glucose, insulin, nonesterified fatty acids, glycerol) were measured at baseline, overnight, and the next morning. RESULTS: There were no differences in overnight SCAAT lipolysis between conditions indicated by interstitial glycerol concentrations (PRO-PLA: baseline, 669 ± 137; next morning, 321 ± 77.1; PLA-PRO: baseline, 524 ± 109; next morning, 333 ± 68.0 µM), fat oxidation (PRO-PLA: baseline, 5.70 ± 0.35; next morning, 5.00 ± 0.28; PLA-PRO: baseline, 6.59 ± 0.32; next morning, 5.44 ± 0.27 g/min), or any other measure. CONCLUSIONS: There was no difference between the effects of daytime and presleep PRO supplementation on SCAAT lipolysis or whole-body substrate utilization in resistance-trained women. Presleep PRO is a viable option for increasing PRO consumption in resistance-trained women because it does not blunt overnight lipolysis, and will therefore likely not lead to increases in subcutaneous abdominal fat.This trial was registered at clinicaltrials.gov as NCT03573687.

Skeletal muscle interstitial fluid metabolomics at rest and associated with an exercise bout: application in rats and humans.

Blood or biopsies are often used to characterize metabolites that are modulated by exercising muscle. However, blood has inputs derived from multiple tissues, biopsies cannot discriminate between secreted and intracellular metabolites, and their invasive nature is challenging for frequent collections in sensitive populations (e.g., children and pregnant women). Thus, minimally invasive approaches to interstitial fluid (IF) metabolomics would be valuable. A catheter was designed to collect IF from the gastrocnemius muscle of acutely anesthetized adult male rats at rest or immediately following 20 min of exercise (~60% of maximal O2 uptake). Nontargeted, gas chromatography-time-of-flight mass spectrometry analysis was used to detect 299 metabolites, including nonannotated metabolites, sugars, fatty acids, amino acids, and purine metabolites and derivatives. Just 43% of all detected metabolites were common to IF and blood plasma, and only 20% of exercise-modified metabolites were shared in both pools, highlighting that the blood does not fully reflect the metabolic outcomes in muscle. Notable exercise patterns included increased IF amino acids (except leucine and isoleucine), increased α-ketoglutarate and citrate (which may reflect tricarboxylic acid cataplerosis or shifts in nonmitochondrial pathways), and higher concentration of the signaling lipid oleamide. A preliminary study of human muscle IF was conducted using a 20-kDa microdialysis catheter placed in the vastus lateralis of five healthy adults at rest and during exercise (65% of estimated maximal heart rate). Approximately 70% of commonly detected metabolites discriminating rest vs. exercise in rats were also changed in exercising humans. Interstitium metabolomics may aid in the identification of molecules that signal muscle work (e.g., exertion and fatigue) and muscle health.

Endothelial Dysfunction: Is There a Hyperglycemia-Induced Imbalance of NOX and NOS?

NADPH oxidases (NOX) are enzyme complexes that have received much attention as key molecules in the development of vascular dysfunction. NOX have the primary function of generating reactive oxygen species (ROS), and are considered the main source of ROS production in endothelial cells. The endothelium is a thin monolayer that lines the inner surface of blood vessels, acting as a secretory organ to maintain homeostasis of blood flow. The enzymatic production of nitric oxide (NO) by endothelial NO synthase (eNOS) is critical in mediating endothelial function, and oxidative stress can cause dysregulation of eNOS and endothelial dysfunction. Insulin is a stimulus for increases in blood flow and endothelium-dependent vasodilation. However, cardiovascular disease and type 2 diabetes are characterized by poor control of the endothelial cell redox environment, with a shift toward overproduction of ROS by NOX. Studies in models of type 2 diabetes demonstrate that aberrant NOX activation contributes to uncoupling of eNOS and endothelial dysfunction. It is well-established that endothelial dysfunction precedes the onset of cardiovascular disease, therefore NOX are important molecular links between type 2 diabetes and vascular complications. The aim of the current review is to describe the normal, healthy physiological mechanisms involved in endothelial function, and highlight the central role of NOX in mediating endothelial dysfunction when glucose homeostasis is impaired.

Interplay Between Workload and Functional Perceptual-Cognitive-Affective Responses: An Inclusive Model.

The extent to and manner in which psychological states change as a function of physical effort and related physiological responses have been addressed separately in various theoretical frameworks. The authors explored a proposed conceptual scheme examining the relationships among perceived exertion, attentional allocation, and affective responses under different workload domains. Thirty male participants performed an incremental cycling test to assess the progression of rating of perceived exertion, attentional focus, affect, and felt arousal along a parallel increase in heart rate using ventilatory threshold as a reference point. Results revealed that ventilatory threshold acts as a metabolic landmark for the attentional shifts toward aversive sensory cues, sustained increases in perceived exertion, negative valence, and physiological activation. Monitoring the dynamics of perceived exertion, attention, and affect can complement physiological measures for an accurate control of training workloads during exercise prescription.

Increase in Lactate Without Change in Nutritive Blood Flow or Glucose at Active Trigger Points Following Massage: A Randomized Clinical Trial.

OBJECTIVE: To investigate changes in nutritive blood flow as well as interstitial glucose and lactate within an active myofascial trigger point (MTrP) following massage. DESIGN: Randomized, placebo-controlled trial. SETTING: Subjects were recruited from the general population; procedures were conducted at a research center affiliated with a university hospital. PARTICIPANTS: Adults (N=25) (18-49y old) with episodic or chronic tension-type headache and an active MTrP in the upper trapezius muscle. INTERVENTIONS: Subjects were randomized to receive a single trigger point (TrP) release massage or sham ultrasound (US) treatment at an active MTrP in the upper trapezius muscle. Microdialysis was used to continuously sample interstitial fluid from the MTrP before, during, and for 60 minutes following intervention. MAIN OUTCOME MEASURES: The primary outcome measure was nutritive blood flow within the MTrP as measured by microdialysis ethanol clearance; secondary measures included dialysate glucose, dialysate lactate, and subject discomfort with the procedures. Pressure-pain threshold (PPT) was determined to assess treatment effectiveness. RESULTS: There was no treatment effect of TrP release massage on nutritive blood flow (P=.663) or dialysate glucose (P=.766). The interaction for lactate was significant indicating that dialysate lactate increased for TrP release massage vs sham US (P=.04); maximum lactate increase over baseline was observed at 60 minutes after TrP release massage (P=.007, 0.128 µM, 95% confidence interval 0.045-0.212). Pain evoked by probe placement into an active MTrP was low. An interaction effect on PPT was significant (P=.005). CONCLUSION: TrP release massage of an active MTrP affected anaerobic metabolism as represented by an increase in dialysate lactate without change in nutritive blood flow or dialysate glucose. The lack of a treatment effect on blood flow is discussed.

Overexpression of PGC-1α increases peroxisomal activity and mitochondrial fatty acid oxidation in human primary myotubes.

Peroxisomes are indispensable organelles for lipid metabolism in humans, and their biogenesis has been assumed to be under regulation by peroxisome proliferator-activated receptors (PPARs). However, recent studies in hepatocytes suggest that the mitochondrial proliferator PGC-1α (peroxisome proliferator-activated receptor gamma coactivator-1α) also acts as an upstream transcriptional regulator for enhancing peroxisomal abundance and associated activity. It is unknown whether the regulatory mechanism(s) for enhancing peroxisomal function is through the same node as mitochondrial biogenesis in human skeletal muscle (HSkM) and whether fatty acid oxidation (FAO) is affected. Primary myotubes from vastus lateralis biopsies from lean donors (BMI = 24.0 ± 0.6 kg/m2; n = 6) were exposed to adenovirus encoding human PGC-1α or GFP control. Peroxisomal biogenesis proteins (peroxins) and genes (PEXs) responsible for proliferation and functions were assessed by Western blotting and real-time qRT-PCR, respectively. [1-14C]palmitic acid and [1-14C]lignoceric acid (exclusive peroxisomal-specific substrate) were used to assess mitochondrial oxidation of peroxisomal-derived metabolites. After overexpression of PGC-1α, 1) peroxisomal membrane protein 70 kDa (PMP70), PEX19, and mitochondrial citrate synthetase protein content were significantly elevated (P < 0.05), 2) PGC-1α, PMP70, key PEXs, and peroxisomal ß-oxidation mRNA expression levels were significantly upregulated (P < 0.05), and 3) a concomitant increase in lignoceric acid oxidation by both peroxisomal and mitochondrial activity was observed (P < 0.05). These novel findings demonstrate that, in addition to the proliferative effect on mitochondria, PGC-1α can induce peroxisomal activity and accompanying elevations in long-chain and very-long-chain fatty acid oxidation by a peroxisomal-mitochondrial functional cooperation, as observed in HSkM cells.

Microvascular Endothelial Dysfunction in Sedentary, Obese Humans Is Mediated by NADPH Oxidase: Influence of Exercise Training.

OBJECTIVE: The objectives of this study were to determine the impact of in vivo reactive oxygen species (ROS) on microvascular endothelial function in obese human subjects and the efficacy of an aerobic exercise intervention on alleviating obesity-associated dysfunctionality. APPROACH AND RESULTS: Young, sedentary men and women were divided into lean (body mass index 18-25; n=14), intermediate (body mass index 28-32.5; n=13), and obese (body mass index 33-40; n=15) groups. A novel microdialysis technique was utilized to detect elevated interstitial hydrogen peroxide (H2O2) and superoxide levels in the vastus lateralis of obese compared with both lean and intermediate subjects. Nutritive blood flow was monitored in the vastus lateralis via the microdialysis-ethanol technique. A decrement in acetylcholine-stimulated blood flow revealed impaired microvascular endothelial function in the obese subjects. Perfusion of apocynin, an NADPH oxidase inhibitor, lowered (normalized) H2O2 and superoxide levels, and reversed microvascular endothelial dysfunction in obese subjects. After 8 weeks of exercise, H2O2 levels were decreased in the obese subjects and microvascular endothelial function in these subjects was restored to levels similar to lean subjects. Skeletal muscle protein expression of the NADPH oxidase subunits p22phox, p47phox, and p67phox was increased in obese relative to lean subjects, where p22phox and p67phox expression was attenuated by exercise training in obese subjects. CONCLUSIONS: This study implicates NADPH oxidase as a source of excessive ROS production in skeletal muscle of obese individuals and links excessive NADPH oxidase-derived ROS to microvascular endothelial dysfunction in obesity. Furthermore, aerobic exercise training proved to be an effective strategy for alleviating these maladies.

Cardiovascular Responses to Unilateral, Bilateral, and Alternating Limb Resistance Exercise Performed Using Different Body Segments.

Moreira, OC, Faraci, LL, de Matos, DG, Mazini Filho, ML, da Silva, SF, Aidar, FJ, Hickner, RC, and de Oliveira, CEP. Cardiovascular responses to unilateral, bilateral and alternating limb resistance exercise performed using different body segments. J Strength Cond Res 31(3): 644-652, 2017-The aim of this study was to verify and compare the cardiovascular responses to unilateral, bilateral, and alternating limb resistance exercise (RE) performed using different body segments. Fifteen men experienced in RE were studied during biceps curls, barbell rows, and knee extension exercises when performed bilaterally, unilaterally, and using alternating limbs. The protocol consisted of 3 sets of 10 repetitions at 80% of 10 repetition maximum with 2-minute rest between sets. Heart rate (HR) and blood pressure (BP) were measured after the last repetition. There was a statistically significant increase in HR, systolic blood pressure (SBP), and rate pressure product (RPP), from rest to postexercise. The RPP was higher in the third set of all exercises and in all 3 forms of execution, when compared with the first set. Bilateral biceps curls caused a greater increase in RPP (first and second sets) and HR, compared with the same exercise performed unilaterally. Furthermore, the performance of bilateral biceps curls induced greater HR and RPP, in all sets, compared with bilateral knee extension and barbell rows. There was also a significantly higher SBP for the alternating second and third sets and also for the bilateral third set of the knee extensions as compared with the barbell rows. It was concluded from the data of this study that the cardiovascular response was increased from rest to postexercise in all forms of exercise, especially immediately after the third set of RE. For exercises performed bilaterally with the upper body (biceps curls), there was a greater cardiovascular response when compared with the same exercise performed unilaterally or with lower-body exercise performed bilaterally.

Pregnancy and Smoothelin-like Protein 1 (SMTNL1) Deletion Promote the Switching of Skeletal Muscle to a Glycolytic Phenotype in Human and Mice.

Pregnancy promotes physiological adaptations throughout the body, mediated by the female sex hormones progesterone and estrogen. Changes in the metabolic properties of skeletal muscle enable the female body to cope with the physiological challenges of pregnancy and may also be linked to the development of insulin resistance. We conducted global microarray, proteomic, and metabolic analyses to study the role of the progesterone receptor and its transcriptional regulator, smoothelin-like protein 1 (SMTNL1) in the adaptation of skeletal muscle to pregnancy. We demonstrate that pregnancy promotes fiber-type changes from an oxidative to glycolytic isoform in skeletal muscle. This phenomenon is regulated through an interaction between SMTNL1 and progesterone receptor, which alters the expression of contractile and metabolic proteins. smtnl1(-/-) mice are metabolically less efficient and show impaired glucose tolerance. Pregnancy antagonizes these effects by inducing metabolic activity and increasing glucose tolerance. Our results suggest that SMTNL1 has a role in mediating the actions of steroid hormones to promote fiber switching in skeletal muscle during pregnancy. Our findings also bear on the management of gestational diabetes that develops as a complication of pregnancy in ~4% of women.

A Randomized Trial Investigating the Influence of Strength Training on Quality of Life in Ischemic Stroke.

BACKGROUND: Strength training post stroke is widely acknowledged as an important part of a rehabilitation program. Muscle strength has been shown to be a significant contributor to physical disability after stroke, which in turn has an immense impact on the reintegration of patients into society, affecting their quality of life. OBJECTIVE: This was a randomized intervention trial to determine the effect of a resistance training program on the quality of life in patients with stroke. METHODS: An experimental group (EG), consisting of 11 subjects aged 51.7 ± 8.0 years, and a control group (CG), consisting of 13 subjects aged 52.5 ± 7.7 years, were studied before and after 12 weeks. EG underwent 12 weeks of strength training three times a week. The CG did not undergo strength training during the 12-week study period. RESULTS: There was a significant increase in quality of life from pre-test to post-test (Δ% = 21.47%; p = 0.021) in EG. There were significant differences in all indicators of quality of life between groups at 12 weeks. There were greater gains in strength in EG than in CG (p ≤ 0.05). There was a negative correlation between the strength gains as determined with the 1RM test and the quality of life, especially in lower limb exercises. CONCLUSION: The results of this study indicate that there was an improvement in the measures of strength in EG, and that there was a correlation between improvements in strength and quality of life in these patients who had previously suffered a stroke at least one year prior to study.

IL-15 concentrations in skeletal muscle and subcutaneous adipose tissue in lean and obese humans: local effects of IL-15 on adipose tissue lipolysis.

Animal/cell investigations indicate that there is a decreased adipose tissue mass resulting from skeletal muscle (SkM) IL-15 secretion (e.g., SkM-blood-adipose tissue axis). IL-15 could regulate fat mass accumulation in obesity via lipolysis, although this has not been investigated in humans. Therefore, the purpose was to examine whether SkM and/or subcutaneous adipose tissue (SCAT) IL-15 concentrations were correlated with SCAT lipolysis in lean and obese humans and determine whether IL-15 perfusion could induce lipolysis in human SCAT. Local SkM and abdominal SCAT IL-15 (microdialysis) and circulating IL-15 (blood) were sampled in lean (BMI: 23.1 ± 1.9 kg/m(2); n = 10) and obese (BMI: 34.7 ± 3.5 kg/m(2); n = 10) subjects at rest/during 1-h cycling exercise. Lipolysis (SCAT interstitial glycerol concentration) was compared against local/systemic IL-15. An additional probe in SCAT was perfused with IL-15 to assess direct lipolytic responses. SkM IL-15 was not different between lean and obese subjects (P = 0.45), whereas SCAT IL-15 was higher in obese vs. lean subjects (P = 0.02) and was correlated with SCAT lipolysis (r = 0.45, P = 0.05). Exercise increased SCAT lipolysis in lean and obese (P < 0.01), but exercise-induced SCAT lipolysis changes were not correlated with exercise-induced SCAT IL-15 changes. Microdialysis perfusion resulting in physiological IL-15 concentrations in the adipose tissue interstitium increased lipolysis in lean (P = 0.04) but suppressed lipolysis in obese (P < 0.01). Although we found no support for a human IL-15 SkM-blood-adipose tissue axis, IL-15 may be produced in/act on the abdominal SCAT depot. The extent to which this autocrine/paracrine IL-15 action regulates human body composition remains unknown.

The Relationship Between Physical Activity and the Metabolic Syndrome Score in Children.

The relationship between physical activity levels and the metabolic syndrome (MetSyn) score was examined in 72 boys and girls (9.5 ± 1.2 years). A fasting blood draw was obtained; waist circumference and blood pressure measured, and an accelerometer was worn for 5 days. Established cut points were used to estimate time spent in moderate, vigorous, moderate-to-vigorous (MVPA), and total physical activity. A continuous MetSyn score was created from blood pressure, waist circumference, high-density-lipoprotein, triglyceride, and glucose values. Regression analysis was used to examine the relationship between physical activity levels, the MetSyn score, and its related components. Logistic regression was used to examine the association between meeting physical activity recommendations, the MetSyn score, and its related components. All analyses were controlled for body mass index group, age, sex, and race. Time spent in different physical activity levels or meeting physical activity recommendations (OR: 0.87, 95%CI: 0.69-1.09) was not related with the MetSyn score after controlling for potential confounders (p > .05). Moderate physical activity, MVPA, and meeting physical activity recommendations were related to a lower diastolic blood pressure (p < .05). No other relationships were observed (p > .05). While physical activity participation was not related with the MetSyn, lower diastolic blood pressure values were related to higher physical activity levels.

Impact of Four Weeks of a Multi-Ingredient Performance Supplement on Muscular Strength, Body Composition, and Anabolic Hormones in Resistance-Trained Young Men.

Although multi-ingredient performance supplements (MIPS) have increased in popularity because of their array of ergogenic ingredients, their efficacy and safety remain in question. The objective of this study was to determine the impact of supplementation with T+ (SUP; Onnit Labs, Austin, TX, USA), an MIPS containing long jack root, beta-alanine, and branched-chain amino acids, and other proprietary blends, on strength, body composition, and hormones in young resistance-trained men. Subjects were randomized to consume either T+ (SUP; n = 14; age, 21 ± 3 years; body fat, 18.3 ± 4.7%) or an isocaloric placebo (PL; n = 13; age, 21 ± 3 years; body fat, 21.5 ± 6.2%) for 4 weeks. Both groups underwent a progressive, 4-week high-intensity resistance training protocol. Before and after the training protocol, mood state, body composition, blood hormones (also collected at midpoint), and maximal strength were measured. SUP had significantly greater increases in bench press (SUP, 102 ± 16 kg to 108 ± 16 kg vs. PL, 96 ± 22 kg to 101 ± 22 kg; p < 0.001) and total weight lifted (SUP, 379 ± 59 kg to 413 ± 60 kg vs. PL, 376 ± 70 kg to 400 ± 75 kg; p < 0.001) compared with PL. Additionally, deadlift strength relative to total body mass (calculated as weight lifted/body mass; kg:kg) (2.08 ± 0.18 to 2.23 ± 0.16; p = 0.036) and lean mass (2.55 ± 0.19 to 2.72 ± 0.16; p = 0.021) increased significantly in SUP but not PL (2.02 ± 0.30 to 2.15 ± 0.36 and 2.56 ± 0.31 to 2.70 ± 0.36, respectively). No other significant differences were detected between groups for the remaining variables. Supplementing with SUP enhanced resistance training adaptations independent of hormonal status, and thus SUP use may warrant inclusion into peri-workout nutrition regimens. This study was registered with clinicaltrials.gov (identifier: NCT01971723).

Assessment of in vivo skeletal muscle mitochondrial respiratory capacity in humans by near-infrared spectroscopy: a comparison with in situ measurements.

The present study aimed to compare in vivo measurements of skeletal muscle mitochondrial respiratory capacity made using near-infrared spectroscopy (NIRS) with the current gold standard, namely in situ measurements of high-resolution respirometry performed in permeabilized muscle fibres prepared from muscle biopsies. Mitochondrial respiratory capacity was determined in 21 healthy adults in vivo using NIRS to measure the recovery kinetics of muscle oxygen consumption following a ∼15 s isometric contraction of the vastus lateralis muscle. Maximal ADP-stimulated (State 3) respiration was measured in permeabilized muscle fibres using high-resolution respirometry with sequential titrations of saturating concentrations of metabolic substrates. Overall, the in vivo and in situ measurements were strongly correlated (Pearson's r = 0.61-0.74, all P < 0.01). Bland-Altman plots also showed good agreement with no indication of bias. The results indicate that in vivo NIRS corresponds well with the current gold standard, in situ high-resolution respirometry, for assessing mitochondrial respiratory capacity.

Sex differences with aging in nutritive skeletal muscle blood flow: impact of exercise training, nitric oxide, and α-adrenergic-mediated mechanisms.

The incidence of cardiovascular disease increases progressively with age, but aging may affect men and women differently. Age-associated changes in vascular structure and function may manifest in impaired nutritive blood flow, although the regulation of nutritive blood flow in healthy aging is not well understood. The purpose of this study was to determine if nitric oxide (NO)-mediated or α-adrenergic-mediated regulation of nutritive skeletal muscle blood flow is impaired with advanced age, and if exercise training improves age-related deficiencies. Nutritive blood flow was monitored in the vastus lateralis of healthy young and aged men and women via the microdialysis-ethanol technique prior to and following seven consecutive days of exercise training. NO-mediated and α-adrenergic-mediated regulation of nutritive blood flow was assessed by microdialysis perfusion of acetylcholine, sodium nitroprusside, N(G)-monomethyl-L-arginine, norepinephrine, or phentolamine. Pretraining nutritive blood flow was attenuated in aged compared with young women (7.39 ± 1.5 vs. 15.5 ± 1.9 ml·100 g(−1)·min(−1), P = 0.018), but not aged men (aged 13.5 ± 3.7 vs. young 9.4 ± 1.3 ml·100 g(−1)·min(−1), P = 0.747). There were no age-associated differences in NO-mediated or α-adrenergic-mediated nutritive blood flow. Exercise training increased resting nutritive blood flow only in young men (9.4 ± 1.3 vs. 19.7 ml·100 g(−1)·min(−1), P = 0.005). The vasodilatory effect of phentolamine was significantly reduced following exercise training only in young men (12.3 ± 6.14 vs. −3.68 ± 3.26 ml·100 g(−1)·min(−1), P = 0.048). In conclusion, the age-associated attenuation of resting nutritive skeletal muscle blood flow was specific to women, while the exercise-induced alleviation of α-adrenergic mediated vasoconstriction that was specific to young men suggests an age-associated modulation of the sympathetic response to exercise training.

Novel role for thioredoxin reductase-2 in mitochondrial redox adaptations to obesogenic diet and exercise in heart and skeletal muscle.

Increased fatty acid availability and oxidative stress are physiological consequences of exercise (Ex) and a high-fat, high-sugar (HFHS) diet. Despite these similarities, the global effects of Ex are beneficial, whereas HFHS diets are largely deleterious to the cardiovascular system. The reasons for this disparity are multifactorial and incompletely understood. We hypothesized that differences in redox adaptations following HFHS diet in comparison to exercise may underlie this disparity, particularly in mitochondria. Our objective in this study was to determine mechanisms by which heart and skeletal muscle (red gastrocnemius, RG) mitochondria experience differential redox adaptations to 12 weeks of HFHS diet and/or exercise training (Ex) in rats. Surprisingly, both HFHS feeding and Ex led to contrasting effects in heart and RG, in that mitochondrial H2O2 decreased in heart but increased in RG following both HFHS diet and Ex, in comparison to sedentary animals fed a control diet. These differences were determined to be due largely to increased antioxidant/anti-inflammatory enzymes in the heart following the HFHS diet, which did not occur in RG. Specifically, upregulation of mitochondrial thioredoxin reductase-2 occurred with both HFHS and Ex in the heart, but only with Ex in RG, and systematic evaluation of this enzyme revealed that it is critical for suppressing mitochondrial H2O2 during fatty acid oxidation. These findings are novel and important in that they illustrate the unique ability of the heart to adapt to oxidative stress imposed by HFHS diet, in part through upregulation of thioredoxin reductase-2. Furthermore, upregulation of thioredoxin reductase-2 plays a critical role in preserving the mitochondrial redox status in the heart and skeletal muscle with exercise.

Estradiol effects on subcutaneous adipose tissue lipolysis in premenopausal women are adipose tissue depot specific and treatment dependent.

Estrogen has direct effects within adipose tissue and has been implicated in regional adiposity; however, the influence of estrogen on in vivo lipolysis is unclear. The purpose of this study was to investigate the effect of local 17ß-estradiol (E(2)) on subcutaneous adipose tissue (SAT) lipolysis in premenopausal women. In vivo lipolysis (dialysate glycerol) was measured in 17 women (age 27.4 ± 2.0 yr, BMI 29.7 ± 0.5 kg/m(2)) via microdialysis of abdominal (AB) and gluteal (GL) SAT. Glycerol was measured at baseline and during acute interventions to increase lipolysis including local perfusion of isoproterenol (ISO, ß-adrenergic agonist, 1.0 µmol/l), phentolamine (PHEN, α-adrenergic antagonist, 0.1 mmol/l), and submaximal exercise (60% Vo(2peak), 30 min); all with and without coperfusion of E(2) (500 nmol/l). E(2) coperfusion blunted the lipolytic response to ISO in AB (E(2) 196 ± 31%, control 258 ± 26%, P = 0.003) but not in GL (E(2) 113 ± 14%, control 111 ± 12%, P = 0.43) adipose tissue. At rest, perfusion of PHEN with ISO did not change dialysate glycerol. Submaximal exercise during ISO + PHEN increased dialysate glycerol in the AB (56 ± 9%) and GL (62 ± 12%) regions. Probes perfused with E(2) during exercise and ISO + PHEN had an increased lipolytic response in AB (90 ± 9%, P = 0.007) but a lower response in GL (35 ± 7%, P = 0.05) SAT compared with no-E(2) conditions. E(2) effects on lipolysis are region specific and may work through both adrenergic and adrenergic-independent mechanisms to potentiate and/or blunt SAT lipolysis in premenopausal women.

Exercise prevents Western diet-associated erectile dysfunction and coronary artery endothelial dysfunction: response to acute apocynin and sepiapterin treatment.

The aim of this study was to investigate aerobic exercise training as a means to prevent erectile dysfunction (ED) and coronary artery disease (CAD) development associated with inactivity and diet-induced obesity. Male Sprague-Dawley rats were fed a Western diet (WD) or a control diet (CD) for 12 wk. Subgroups within each diet remained sedentary (Sed) or participated in aerobic interval treadmill running throughout the dietary intervention. Erectile function was evaluated under anesthesia by measuring the mean arterial pressure and intracavernosal pressure in response to electrical field stimulation of the cavernosal nerve, in the absence or presence of either apocynin, an NADPH oxidase inhibitor, or sepiapterin, a tetrahydrobiopterin precursor. Coronary artery endothelial function (CAEF) was evaluated ex vivo with cumulative doses of ACh applied to preconstricted segments of the left anterior descending coronary artery. CAEF was assessed in the absence or presence of apocynin or sepiapterin. Erectile function (P < 0.0001) and CAEF (P < 0.001) were attenuated in WD-Sed. Exercise preserved erectile function (P < 0.0001) and CAEF (P < 0.05) within the WD. Erectile function (P < 0.01) and CAEF (P < 0.05) were augmented by apocynin only in WD-Sed, while sepiapterin (P < 0.05) only augmented erectile function in WD-Sed. These data demonstrate that a chronic WD induces impairment in erectile function and CAEF that are commonly partially reversible by apocynin, whereas sepiapterin treatment exerted differential functional effects between the two vascular beds. Furthermore, exercise training may be a practical means of preventing diet-induced ED and CAD development.