Collagen peptides supplementation improves function, pain, and physical and mental outcomes in active adults.

INTRODUCTION: Chronic pain affects 19% of adults in the United States, with increasing prevalence in active and aging populations. Pain can limit physical activity and activities of daily living (ADLs), resulting in declined mental and social health. Nutritional interventions for pain currently target inflammation or joint health, but few influence both. Collagen, the most abundant protein in the human body and constituent of the extra cellular matrix, is such a nutraceutical. While there have been reports of reductions in pain with short-term collagen peptide (CP) supplementation, there are no long-term studies specifically in healthy middle-aged active adults. PURPOSE: To determine the effects of daily CP consumption over 3, 6, and 9 months on survey measures of pain, function, and physical and mental health using The Knee Injury & Osteoarthritis Outcomes Score (KOOS) and Veterans Rand 12 (VR-12) in middle-aged active adults. METHODS: This study was a double-blind randomized control trial with three treatment groups (Placebo, 10 g/d CP, and 20 g/d CP). RESULTS: Improvements in ADLs (p = .031, ηp2 = .096) and pain (p = .037, ηp2 = .164) were observed with 10 g/d CP over 6 months, although pain only improved in high frequency exercisers (>180 min/week). Additionally, VR-12 mental component scores (MCS) improved with 10 g/d of CP over 3-9 months (p = .017, ηp2 = .309), while physical component scores (PCS) improved with 20 g/d of CP over 3-9 months, but only in females (p = .013, ηp2= .582). CONCLUSION: These findings suggest 10 to 20 g/d of CP supplementation over 6 to 9 months may improve ADLs, pain, MCS, and PCS in middle-aged active adults.

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.

The Short-Term Effect of Prunes in Improving Bone in Men.

Osteoporosis is a major health concern in aging populations, where 54% of the U.S. population aged 50 and older have low bone mineral density (BMD). Increases in inflammation and oxidative stress play a major role in the development of osteoporosis. Men are at a greater risk of mortality due to osteoporosis-related fractures. Our earlier findings in rodent male and female models of osteoporosis, as well as postmenopausal women strongly suggest the efficacy of prunes (dried plum) in reducing inflammation and preventing/reversing bone loss. The objective of this study was to examine the effects of two doses of prunes, daily, on biomarkers of inflammation and bone metabolism in men with some degree of bone loss (BMD; t-score between -0.1 and -2.5 SD), for three months. Thirty-five men between the ages of 55 and 80 years were randomized into one of three groups: 100 g prunes, 50 g prunes, or control. Consumption of 100 g prunes led to a significant decrease in serum osteocalcin (p < 0.001). Consumption of 50 g prunes led to significant decreases in serum osteoprotegerin (OPG) (p = 0.003) and serum osteocalcin (p = 0.040), and an increase in the OPG:RANKL ratio (p = 0.041). Regular consumption of either 100 g or 50 g prunes for three months may positively affect bone turnover.

Systemic delivery of a mitochondria targeted antioxidant partially preserves limb muscle mass and grip strength in response to androgen deprivation.

Muscle mass is important for health. Decreased testicular androgen production (hypogonadism) contributes to the loss of muscle mass, with loss of limb muscle being particularly debilitating. Androgen replacement is the only pharmacological treatment, which may not be feasible for everyone. Prior work showed that markers of reactive oxygen species and markers of mitochondrial degradation pathways were higher in the limb muscle following castration. Therefore, we tested whether an antioxidant preserved limb muscle mass in male mice subjected to a castration surgery. Subsets of castrated mice were treated with resveratrol (a general antioxidant) or MitoQ (a mitochondria targeted antioxidant). Relative to the non-castrated control mice, lean mass, limb muscle mass, and grip strength were partially preserved only in castrated mice treated with MitoQ. Independent of treatment, markers of mitochondrial degradation pathways remained elevated in all castrated mice. Therefore, a mitochondrial targeted antioxidant may partially preserve limb muscle mass in response to hypogonadism.

Peroxisomal gene and protein expression increase in response to a high-lipid challenge in human skeletal muscle.

Peroxisomes are essential for lipid metabolism and disruption of liver peroxisomal function results in neonatal death. Little is known about how peroxisomal content and activity respond to changes in the lipid environment in human skeletal muscle (HSkM). AIMS: We hypothesized and tested that increased peroxisomal gene/protein expression and functionality occur in HSkM as an adaptive response to lipid oversupply. MATERIALS AND METHODS: HSkM biopsies, derived from a total of sixty-two subjects, were collected for 1) examining correlations between peroxisomal proteins and intramyocellular lipid content (IMLC) as well as between peroxisomal functionality and IMLC, 2) assessing peroxisomal gene expression in response to acute- or 7-day high fat meal (HFM), and in human tissue derived primary myotubes for 3) treating with high fatty acids to induce peroxisomal adaptions. IMLC were measured by both biochemical analyses and fluorescent staining. Peroxisomal membrane protein PMP70 and biogenesis gene (PEX) expression were assessed using western blotting and realtime qRT-PCR respectively. 1-14C radiolabeled lignocerate and palmitate oxidation assays were performed for peroxisomal and mitochondrial functionality respectively. RESULTS: 1) Under fasting conditions, HSkM tissue demonstrated a significant correlation (P ≪ 0.05) between IMCL and the peroxisomal biogenesis factor 19 (PEX19) protein as well as between lipid content and palmitate and lignocerate complete oxidation. 2) Similarly, post-HFM, additional PEX genes (Pex19, PEX11A, and PEX5) were significantly (P ≪ 0.05) upregulated. 3) Increments in PMP70, carnitine octanoyl transferase (CrOT), PGC-1α, and ERRα mRNA were observed post-fatty acid incubation in HSkM cells. PMP70 protein was significantly (P ≪ 0.05) elevated 48-h post lipid treatment. CONCLUSIONS: These results are the first to associate IMLC with peroxisomal gene/protein expression and function in HSkM suggesting an adaptive role for peroxisomes in lipid metabolism in this tissue.

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.

Prevalence of coronary heart disease risk factors in physical education students / Prevalência de fatores de risco de doença coronariana em estudantes de educação física / Prevalencia de factores de riesgo de enfermedad coronaria en los estudiantes de educación física

To establish the prevalence of coronary risk in physical education students, and compare risk between the genders and the years of course. We evaluated 246 physical education students using RISKO questionnaire to determine eight risk factors: age, heredity, body weight, smoking, physical inactivity, hypercholesterolemia, hypertension and sex. Students had mean coronary risk score of 16.03 ± 3.52 points, rated "below-average risk." Men had significantly greater risk compared to women. No difference was found between the years of course. The prevalence of risk factors were heritability (58.37%), physical inactivity (32.65%), hypercholesterolemia (32.24%), overweight (27.35%), smoking (3.67%) and hypertension (2.45%). The coronary risk of physical education students was rated as below average, being higher among men than women, and no difference in risk between years of course. The most prevalent risk factors were heredity, physical inactivity, overweight and hypercholesterolemia.

Estabelecer a prevalência de risco coronariano em estudantes de educação física, e comparar o risco entre os gêneros e os anos de curso. 246 estudantes de educação física foram avaliados por questionário Risko, que avalia oito fatores de risco: idade, hereditariedade, peso corporal, tabagismo, inatividade física, hipercolesterolemia, hipertensão e sexo. Os alunos tiveram média do escore de risco coronariano de 16,03 ± 3,52 pontos, classificados como "de risco abaixo da média." Os homens tiveram risco significativamente maior em comparação com as mulheres. Não foram encontradas diferenças entre os anos de curso. A prevalência de fatores de risco foram herdabilidade (58,37%), inatividade física (32,65%), hipercolesterolemia (32,24%), sobrepeso (27,35%), fumo (3,67%) e hipertensão arterial (2,45%). O risco coronariano de estudantes de educação física foi classificada como abaixo da média, sendo maior entre os homens do que as mulheres, e não houve diferença no risco entre os anos de curso. Os fatores de risco mais prevalentes foram hereditariedade, sedentarismo, excesso de peso e hipercolesterolemia.

Establecer la prevalencia del riesgo cardiovascular en estudiantes de educación física y comparar el riesgo entre los géneros y los años del curso. 246 estudiantes de educación física fueron evaluados por el cuestionario RISKO, que valora ocho factores de riesgo: edad, hereditadiedad, peso corporal, tabaquismo, inactividad física, hipercolesterolemia, hipertensión arterial y sexo. El promedio de riesgo cardiovascular de los estudioantes fue 16.03 ± 3.52 puntos, clasificado como "riesgo bajo el promedio." Los hombres presentaron riesgo significantemente más grande que las mujeres. No fueron encontradas diferencias en el riesgo para los años del curso. Los factores de riesgo más prevalentes fueron hereditariedad (58,37%), inactividad física (32,65%), hipercolesterolemia (32,24%), sobrepeso (27,35%), tabaquismo (3,67%) y hipertensión arterial (2,45%). El riesgo cardiovacular de los estudiantes de educación física fue clasificado como bajo el promedio, presentandose más elevado en los hombres y sin diferencias entre los años del curso. Los factores más prevalentes fueron hereditariedad, inactividad física, sobrepeso y hipercolesterolemia.

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.

Lung protective ventilation (ARDSNet) versus airway pressure release ventilation: ventilatory management in a combined model of acute lung and brain injury.

BACKGROUND: Concomitant lung/brain traumatic injury results in significant morbidity and mortality. Lung protective ventilation (Acute Respiratory Distress Syndrome Network [ARDSNet]) has become the standard for managing adult respiratory distress syndrome; however, the resulting permissive hypercapnea may compound traumatic brain injury. Airway pressure release ventilation (APRV) offers an alternative strategy for the management of this patient population. APRV was hypothesized to retard the progression of acute lung/brain injury to a degree greater than ARDSNet in a swine model. METHODS: Yorkshire swine were randomized to ARDSNet, APRV, or sham. Ventilatory settings and pulmonary parameters, vitals, blood gases, quantitative histopathology, and cerebral microdialysis were compared between groups using χ2, Fisher's exact, Student's t test, Wilcoxon rank-sum, and mixed-effects repeated-measures modeling. RESULTS: Twenty-two swine (17 male, 5 female), weighing a mean (SD) of 25 (6.0) kg, were randomized to APRV (n = 9), ARDSNet (n = 12), or sham (n = 1). PaO2/FIO2 ratio dropped significantly, while intracranial pressure increased significantly for all three groups immediately following lung and brain injury. Over time, peak inspiratory pressure, mean airway pressure, and PaO2/FIO2 ratio significantly increased, while total respiratory rate significantly decreased within the APRV group compared with the ARDSNet group. Histopathology did not show significant differences between groups in overall brain or lung tissue injury; however, cerebral microdialysis trends suggested increased ischemia within the APRV group compared with ARDSNet over time. CONCLUSION: Previous studies have not evaluated the effects of APRV in this population. While our macroscopic parameters and histopathology did not observe a significant difference between groups, microdialysis data suggest a trend toward increased cerebral ischemia associated with APRV over time. Additional and future studies should focus on extending the time interval for observation to further delineate differences between groups.

Aging and the Skeletal Muscle Angiogenic Response to Exercise in Women.

Whether aging lowers skeletal muscle basal capillarization and angiogenesis remains controversial. To investigate the effects of aging on skeletal muscle capillarization, eight young (YW) and eight aged (AW) women completed 8 weeks of exercise training. The response and relationships of muscle capillarization, interstitial vascular endothelial growth factor (VEGF), and microvascular blood flow to aerobic exercise training were investigated. Vastus lateralis biopsies were obtained before and after exercise training for the measurement of capillarization. Muscle interstitial VEGF protein and microvascular blood flow were measured at rest and during submaximal exercise at PRE, 1-WK, and 8-WKS by microdialysis. Exercise training increased (20%-25%) capillary contacts of type I, IIA, and IIB fibers in YW and AW. Interstitial VEGF protein was higher in AW than YW at rest and was higher in YW than AW during exercise independent of training status. Differences in muscle capillarization were not explained by secreted VEGF nor were differences in VEGF explained by microvascular blood flow. These results confirm that aging (57-76 years age range) does not impair the muscle angiogenic response to exercise training, although sex differences may exist in similarly trained women and men.

Motivational climate, goal orientation and exercise adherence in fitness centers and personal training contexts / Clima motivacional, orientação para a meta e exercício adesão em academias de ginástica e contextos de formação pessoal / Clima motivacional, la orientación de meta y la adherencia al ejercicio en gimnasios y contextos de entrenamiento personal

This study was conducted to analyze the relationships hypothesized by the Achievement Goal Theory in predicting adherence to exercise. The study participants were 405 individuals exercising in fitness centers with a mean age of 35 years (SD = 17) and 183 individuals exercising with personal trainers with a mean age of 43 years (SD = 16), that answered the Portuguese versions of the Goal Orientation in Exercise Measure and Perceived Motivational Climate in Exercise Questionnaire. The hypothesized structural equation model showed that the mastery motivational climate had a positive impact on task orientation goals, which in turn had a positive impact on exercise adherence. However, performance motivational climate had a positive impact on ego orientation goals, which in turn had a negative impact on exercise adherence...

"Clima motivacional, orientação para a meta e exercício adesão em academias de ginástica e contextos de formação pessoal." Este estudo analisou as relações hipotetizadas pela Teoria dos Objetivos de Realização na predição da adesão ao exercício. Participaram neste estudo 405 praticantes de academia (240 femininos, 165 masculinos), com uma média de idades de 35 anos (DP = 17) e 183 de personal training (142 femininos, 41 masculinos), com uma média de idades de 43 anos (DP = 16), que responderam às versões Portuguesas do Goal Orientation in Exercise Measure e Perceived Motivational Climate in Exercise Questionnaire. O modelo de equações estruturais demonstra que o clima motivacional para a mestria teve um impacto positivo sobre a orientação dos objetivos para a tarefa, que por sua vez teve um impacto positivo sobre a adesão ao exercício. Por outro lado, o clima motivacional para a performance teve um impacto positivo sobre a orientação dos objetivos para o ego, que por sua vez teve um impacto negativo sobre a adesão ao exercício...

"Clima motivacional, la orientación de meta y la adherencia al ejercicio en gimnasios y contextos de entrenamiento personal." Este estudio analizó las relaciones hipotetizadas por la Teoría de los Objetivos de Realización en la predicción de la adhesión al ejercicio. En este estudio participaron 405 practicantes de academia (240 femeninos, 165 masculinos), con una edad media de 35 años (DP = 17) y 183 de personal training (142 femeninos, 41 masculinos), con una edad media de 43 años (DP = 16), que respondieron a las versiones portuguesas de Goal Orientation in Exercise Measure y Perceived Motivational Climate in Exercise Questionnaire. El modelo de ecuaciones estructurales demuestra que el clima motivacional para la maestría tuvo un impacto positivo sobre la orientación de los objetivos para la tarea que, a su vez, tuvo un impacto positivo sobre la adhesión al ejercicio. Por otro lado, el clima motivacional para la performance tuvo un impacto positivo sobre la orientación de los objetivos para el ego que, a su vez, tuvo un impacto negativo sobre la adhesión al ejercicio....

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.

Estrogen receptor protein content is different in abdominal than gluteal subcutaneous adipose tissue of overweight-to-obese premenopausal women.

OBJECTIVE: Premenopausal women demonstrate a distinctive gynoid body fat distribution and circulating estrogen status is associated with the maintenance of this adiposity patterning. Estrogen's role in modulation of regional adiposity may occur through estrogen receptors (ERs), which are present in human adipose tissue. The purpose of this study was to determine regional differences in the protein content of ERα, ERß, and the G protein-coupled estrogen receptor (GPER) between the abdominal (AB) and gluteal (GL) subcutaneous adipose tissue of overweight-to-obese premenopausal women. MATERIALS/METHODS: Biopsies of the subcutaneous AB and GL adipose tissue were performed in 15 premenopausal women (7 Caucasian/8 African American, 25.1 ± 1.8 years, BMI 29.5 ± 0.5kg/m(2)). Adipose tissue protein content was measured by western blot analysis and correlation analyses were conducted to assess the relationship between ER protein content and anthropometric indices/body composition measurements. RESULTS: We found that ERα protein was higher in AB than GL (AB 1.0 ± 0.2 vs GL 0.67 ± 0.1 arbitrary units [AU], P=0.02), ERß protein was higher in GL than AB (AB 0.78 ± 0.12 vs GL 1.3 ± 0.2 AU, P=0.002), ERα/ERß ratio was higher in AB than GL (AB 1.9 ± 0.4 vs GL 0.58 ± 0.08 AU, P=0.007), and GPER protein content was similar in AB and GL (P=0.80) subcutaneous adipose tissue. Waist-to-hip ratio was inversely related to gluteal ERß (r(2)=0.315, P=0.03) and positively related to gluteal ERα/ERß ratio (r(2)=0.406, P=0.01). CONCLUSIONS: These results indicate that depot specific ER content may be an important underlying determinant of regional effects of estrogen in upper and lower body adipose tissue of overweight-to-obese premenopausal women.

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.

Effect of exercise training on metabolic flexibility in response to a high-fat diet in obese individuals.

Obese individuals typically exhibit a reduced capacity for metabolic flexibility by failing to increase fatty acid oxidation (FAO) upon the imposition of a high-fat diet (HFD). Exercise training increases FAO in the skeletal muscle of obese individuals, but whether this intervention can restore metabolic flexibility is unclear. The purpose of this study was to compare FAO in the skeletal muscle of lean and obese subjects in response to a HFD before and after exercise training. Twelve lean (means ± SE) (age 21.8 ± 1.1 yr, BMI 22.6 ± 0.7 kg/m²) and 10 obese men (age 22.4 ± 0.8 yr, BMI 33.7 ± 0.7 kg/m²) consumed a eucaloric HFD (70% of energy from fat) for 3 days. After a washout period, 10 consecutive days of aerobic exercise (1 h/day, 70% V(O2(peak))) were performed, with the HFD repeated during days 8-10. FAO and indices of mitochondrial content were determined from muscle biopsies. In response to the HFD, lean subjects increased complete FAO (27.3 ± 7.4%, P = 0.03) in contrast to no change in their obese counterparts (1.0 ± 7.9%). After 7 days of exercise, citrate synthase activity and FAO increased (P < 0.05) regardless of body habitus; addition of the HFD elicited no further increase in FAO. These data indicate that obese, in contrast to lean, individuals do not increase FAO in skeletal muscle in response to a HFD. The increase in FAO with exercise training, however, enables the skeletal muscle of obese individuals to respond similarly to their lean counterparts when confronted with short-term excursion in dietary lipid.

Progesterone increases skeletal muscle mitochondrial H2O2 emission in nonmenopausal women.

The luteal phase of the female menstrual cycle is associated with both 1) elevated serum progesterone (P4) and estradiol (E2), and 2) reduced insulin sensitivity. Recently, we demonstrated a link between skeletal muscle mitochondrial H(2)O(2) emission (mE(H2O2)) and insulin resistance. To determine whether serum levels of P4 and/or E(2) are related to mitochondrial function, mE(H2O2) and respiratory O(2) flux (Jo(2)) were measured in permeabilized myofibers from insulin-sensitive (IS, n = 24) and -resistant (IR, n = 8) nonmenopausal women (IR = HOMA-IR > 3.6). Succinate-supported mE(H2O2) was more than 50% greater in the IR vs. IS women (P < 0.05). Interestingly, serum P4 correlated positively with succinate-supported mE(H2O2) (r = 0. 53, P < 0.01). To determine whether P4 or E2 directly affect mitochondrial function, saponin-permeabilized vastus lateralis myofibers biopsied from five nonmenopausal women in the early follicular phase were incubated in P4 (60 nM), E2 (1.4 nM), or both. P4 alone inhibited state 3 Jo(2), supported by multisubstrate combination (P < 0.01). However, E2 alone or in combination with P4 had no effect on Jo(2). In contrast, during state 4 respiration, supported by succinate and glycerophosphate, mE(H2O2) was increased with P4 alone or in combination with E2 (P < 0.01). The results suggest that 1) P4 increases mE(H2O2) with or without E2; 2) P4 alone inhibits Jo(2) but not when E2 is present; and 3) P4 is related to the mE(H2O2) previously linked to skeletal muscle insulin resistance.

Lipid-induced insulin resistance is prevented in lean and obese myotubes by AICAR treatment.

The molecular mechanisms of obesity-associated insulin resistance are becoming increasingly clear, and the effects of various lipid molecules, such as diacylglycerol and ceramide, on the insulin signal are being actively explored. To better understand the divergent response to lipid exposure between lean and obese, we incubated primary human muscle cells from lean [body mass index (BMI) <25 kg/m(2)] and morbidly obese (BMI >40 kg/m(2)) subjects with the saturated fatty acid palmitate. Additionally, given that AMPK-activating drugs are widely prescribed for their insulin-sensitizing effects, we sought to determine whether 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside (AICAR)-stimulated AMPK activation could prevent or reverse the deleterious effects of lipid on insulin signaling. We found that a 1-h palmitate incubation in lean myotubes reduced (P < 0.05) insulin-stimulated phosphoprotein kinase B (Akt), Akt substrate 160 (AS160), and inhibitory factor kappaBalpha (IkappaBalpha) mass, all of which were prevented with AICAR inclusion. With a longer incubation, we observed that myotubes from morbidly obese individuals appear to be largely resistant to the detrimental effects of 16 h lipid exposure as was evident, in contrast to the lean, by the absence of a reduction in insulin-stimulated insulin receptor substrate (IRS)-1 Tyr phosphorylation, phospho-Akt, and phospho-AS160 (P < 0.05). Furthermore, 16 h lipid exposure significantly reduced IkappaBalpha levels and increased phosphorylation of c-Jun NH(2)-terminal kinase (JNK) and IRS1-Ser(312) in lean myotubes only (P < 0.05). Despite a divergent response to lipid between lean and obese myotubes, AICAR inclusion improved insulin signaling in all myotubes. These findings suggest an important role for regular exercise in addition to offering a potential mechanism of action for oral AMPK-activating agents, such as thiazolidinediones and metformin.

Deletion of the protein kinase A/protein kinase G target SMTNL1 promotes an exercise-adapted phenotype in vascular smooth muscle.

In vivo protein kinases A and G (PKA and PKG) coordinately phosphorylate a broad range of substrates to mediate their various physiological effects. The functions of many of these substrates have yet to be defined genetically. Herein we show a role for smoothelin-like protein 1 (SMTNL1), a novel in vivo target of PKG/PKA, in mediating vascular adaptations to exercise. Aortas from smtnl1(-/-) mice exhibited strikingly enhanced vasorelaxation before exercise, similar in extent to that achieved after endurance training of wild-type littermates. Additionally, contractile responses to alpha-adrenergic agonists were greatly attenuated. Immunological studies showed SMTNL1 is expressed in smooth muscle and type 2a striated muscle fibers. Consistent with a role in adaptations to exercise, smtnl1(-/-) mice also exhibited increased type 2a fibers before training and better performance after forced endurance training compared smtnl1(+/+) mice. Furthermore, exercise was found to reduce expression of SMTNL1, particularly in female mice. In both muscle types, SMTNL1 is phosphorylated at Ser-301 in response to adrenergic signals. In vitro SMTNL1 suppresses myosin phosphatase activity through a substrate-directed effect, which is relieved by Ser-301 phosphorylation. Our findings suggest roles for SMTNL1 in cGMP/cAMP-mediated adaptations to exercise through mechanisms involving direct modulation of contractile activity.

No difference in the skeletal muscle angiogenic response to aerobic exercise training between young and aged men.

Ischaemia-induced skeletal muscle angiogenesis is impaired in aged compared with young mice. In humans, vascular endothelial growth factor (VEGF) mRNA and protein following an acute exercise bout are lower in aged compared with young untrained men. We hypothesized that exercise-induced skeletal muscle angiogenesis would be attenuated in aged compared with young men. In eight aged (mean age: 64 years) and six young (mean age: 25 years) sedentary men, muscle biopsies were obtained from the vastus lateralis prior to (Pre), after 1 week and after 8 weeks of an aerobic exercise training program for the measurement of capillarization and VEGF mRNA. Dialysate VEGF protein collected from the muscle interstitial space was measured at rest and during submaximal exercise at Pre, 1 week and 8 weeks. Exercise training increased capillary contacts (CC) and capillary-to-fibre perimeter exchange index (CFPE) of type I and IIA fibres similarly in young and aged. The CC of type IIA and IIB fibres was lower in aged compared with young independent of training status. Exercise-induced interstitial VEGF protein was lower in aged compared with young independent of training status. In untrained, greater exercise-induced interstitial VEGF protein during exercise was associated with greater type I, IIA and IIB CC. Exercise training increased VEGF mRNA similarly in young and aged. These results demonstrate that the angiogenic response to aerobic exercise training is not altered during the ageing process in humans. In addition, muscular activity-associated increases in interstitial VEGF protein may play an important role in the maintenance of skeletal muscle capillarization across the life span.