What We Do Not Know About Stretching in Healthy Athletes: A Scoping Review with Evidence Gap Map from 300 Trials.

BACKGROUND: Stretching has garnered significant attention in sports sciences, resulting in numerous studies. However, there is no comprehensive overview on investigation of stretching in healthy athletes. OBJECTIVES: To perform a systematic scoping review with an evidence gap map of stretching studies in healthy athletes, identify current gaps in the literature, and provide stakeholders with priorities for future research. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 and PRISMA-ScR guidelines were followed. We included studies comprising healthy athletes exposed to acute and/or chronic stretching interventions. Six databases were searched (CINAHL, EMBASE, PubMed, Scopus, SPORTDiscus, and Web of Science) until 1 January 2023. The relevant data were narratively synthesized; quantitative data summaries were provided for key data items. An evidence gap map was developed to offer an overview of the existing research and relevant gaps. RESULTS: Of ~ 220,000 screened records, we included 300 trials involving 7080 athletes [mostly males (~ 65% versus ~ 20% female, and ~ 15% unreported) under 36 years of age; tiers 2 and 3 of the Participant Classification Framework] across 43 sports. Sports requiring extreme range of motion (e.g., gymnastics) were underrepresented. Most trials assessed the acute effects of stretching, with chronic effects being scrutinized in less than 20% of trials. Chronic interventions averaged 7.4 ± 5.1 weeks and never exceeded 6 months. Most trials (~ 85%) implemented stretching within the warm-up, with other application timings (e.g., post-exercise) being under-researched. Most trials examined static active stretching (62.3%), followed by dynamic stretching (38.3%) and proprioceptive neuromuscular facilitation (PNF) stretching (12.0%), with scarce research on alternative methods (e.g., ballistic stretching). Comparators were mostly limited to passive controls, with ~ 25% of trials including active controls (e.g., strength training). The lower limbs were primarily targeted by interventions (~ 75%). Reporting of dose was heterogeneous in style (e.g., 10 repetitions versus 10 s for dynamic stretching) and completeness of information (i.e., with disparities in the comprehensiveness of the provided information). Most trials (~ 90%) reported performance-related outcomes (mainly strength/power and range of motion); sport-specific outcomes were collected in less than 15% of trials. Biomechanical, physiological, and neural/psychological outcomes were assessed sparsely and heterogeneously; only five trials investigated injury-related outcomes. CONCLUSIONS: There is room for improvement, with many areas of research on stretching being underexplored and others currently too heterogeneous for reliable comparisons between studies. There is limited representation of elite-level athletes (~ 5% tier 4 and no tier 5) and underpowered sample sizes (≤ 20 participants). Research was biased toward adult male athletes of sports not requiring extreme ranges of motion, and mostly assessed the acute effects of static active stretching and dynamic stretching during the warm-up. Dose-response relationships remain largely underexplored. Outcomes were mostly limited to general performance testing. Injury prevention and other effects of stretching remain poorly investigated. These relevant research gaps should be prioritized by funding policies. REGISTRATION: OSF project ( https://osf.io/6auyj/ ) and registration ( https://osf.io/gu8ya ).

Adherence to the Mediterranean diet in young male soccer players.

INTRODUCTION: Nutrition is vital in health and sports performance by improving anthropometric-related parameters and dietary habits, especially in the youngest ages. The Mediterranean diet (MD) has been highly recognized for its positive health effects and low adverse environmental impact. OBJECTIVES: We aimed to characterize adherence to the MD and analyze its association with anthropometric parameters in young soccer players. METHODOLOGY: In the present study, 132 male young soccer players from under 9 to under 15 categories (aged 7 to 15 years) from a Portuguese football club participated. The Mediterranean Diet Quality Index for Children and Adolescents (KIDMED) questionnaire was applied to assess adherence to the MD. Anthropometric-related parameters, including body mass, height, triceps skinfold thickness (TSKF), suprailiac skinfold thickness (SISKF), body mass index (BMI) and body fat percentage (%BF), were determined. The differences between groups were performed accordingly to normal and non-normal distribution. Spearman's correlations were performed to analyze the hypothetical correlation between KIDMED and BMI. RESULTS: Players reached an average KIDMED score of 8.36 ± 1.92, showing that 68.2% (n = 90) reached high adherence to the MD, 31.1% (n = 41) had moderate adherence to the MD, and 0.78% (n = 1) had poor adherence to the MD. When the analysis was made for age group and BMI classification, no significant differences were observed in adherence to the MD. Considering the main characteristics of the MD, 50.8% consumed fruit (vs. 49,2%), 52.3% consumed vegetables (vs. 47,7%), and only 20% consumed oleaginous dried fruits (vs. 80%). Dairy consumption throughout the day was 49,2% (vs. no: 50,8%). CONCLUSION: Data from the present study showed that many soccer players adhered to the MD, and no differences were observed for age group or BMI classification.

Effectiveness of Conservative Interventions After Acute Hamstrings Injuries in Athletes: A Living Systematic Review.

BACKGROUND: Hamstrings injuries are common in sports and the reinjury risk is high. Despite the extensive literature on hamstrings injuries, the effectiveness of the different conservative (i.e., non-surgical) interventions (i.e., modalities and doses) for the rehabilitation of athletes with acute hamstrings injuries is unclear. OBJECTIVE: We aimed to compare the effects of different conservative interventions in time to return to sport (TRTS) and/or time to return to full training (TRFT) and reinjury-related outcomes after acute hamstrings injuries in athletes. DATA SOURCES: We searched CINAHL, Cochrane Library, EMBASE, PubMed, Scopus, SPORTDiscus, and Web of Science databases up to 1 January, 2022, complemented with manual searches, prospective citation tracking, and consultation of external experts. ELIGIBILITY CRITERIA: The eligibility criteria were multi-arm studies (randomized and non-randomized) that compared conservative treatments of acute hamstrings injuries in athletes. DATA ANALYSIS: We summarized the characteristics of included studies and conservative interventions and analyzed data for main outcomes (TRTS, TRFT, and rate of reinjuries). The risk of bias was judged using the Cochrane tools. Quality and completeness of reporting of therapeutic exercise programs were appraised with the i-CONTENT tool and the certainty of evidence was judged using the GRADE framework. TRTS and TRFT were analyzed using mean differences and the risk of reinjury with relative risks. RESULTS: Fourteen studies (12 randomized and two non-randomized) comprising 730 athletes (mostly men with ages between 14 and 49 years) from different sports were included. Nine randomized studies were judged at high risk and three at low risk of bias, and the two non-randomized studies were judged at critical risk of bias. Seven randomized studies compared exercise-based interventions (e.g., L-protocol vs C-protocol), one randomized study compared the use of low-level laser therapy, and three randomized and two non-randomized studies compared injections of platelet-rich plasma to placebo or no injection. These low-level laser therapy and platelet-rich plasma studies complemented their interventions with an exercise program. Only three studies were judged at low overall risk of ineffectiveness (i-CONTENT). No single intervention or combination of interventions proved superior in achieving a faster TRTS/TRFT or reducing the risk of reinjury. Only eccentric lengthening exercises showed limited evidence in allowing a shorter TRFT. The platelet-rich plasma treatment did not consistently reduce the TRFT or have any effect on the risk of new hamstrings injuries. The certainty of evidence was very low for all outcomes and comparisons. CONCLUSIONS: Available evidence precludes the prioritization of a particular exercise-based intervention for athletes with acute hamstrings injuries, as different exercise-based interventions showed comparable effects on TRTS/TRFT and the risk of reinjuries. Available evidence also does not support the use of platelet-rich plasma or low-level laser therapy in clinical practice. The currently available literature is limited because of the risk of bias, risk of ineffectiveness of exercise protocols (as assessed with the i-CONTENT), and the lack of comparability across existing studies. CLINICAL TRIAL REGISTRATION: PROSPERO CRD42021268499 and OSF ( https://osf.io/3k4u2/ ).

Nutrition and Physical Exercise in Women.

While the benefits of nutrition and physical exercise are commonly studied separately, their concomitant integration has the potential to produce greater benefits in women than strategies focusing only on one or the other [...].

Multimodal Benefits of Exercise in Patients With Multiple Sclerosis and COVID-19.

Multiple sclerosis (MS) is a demyelinating disease characterized by plaque formation and neuroinflammation. The plaques can present in various locations, causing a variety of clinical symptoms in patients with MS. Coronavirus disease-2019 (COVID-19) is also associated with systemic inflammation and a cytokine storm which can cause plaque formation in several areas of the brain. These concurring events could exacerbate the disease burden of MS. We review the neuro-invasive properties of SARS-CoV-2 and the possible pathways for the entry of the virus into the central nervous system (CNS). Complications due to this viral infection are similar to those occurring in patients with MS. Conditions related to MS which make patients more susceptible to viral infection include inflammatory status, blood-brain barrier (BBB) permeability, function of CNS cells, and plaque formation. There are also psychoneurological and mood disorders associated with both MS and COVID-19 infections. Finally, we discuss the effects of exercise on peripheral and central inflammation, BBB integrity, glia and neural cells, and remyelination. We conclude that moderate exercise training prior or after infection with SARS-CoV-2 can produce health benefits in patients with MS patients, including reduced mortality and improved physical and mental health of patients with MS.

Nutritional Intake and Training Load of Professional Female Football Players during a Mid-Season Microcycle.

Football (soccer) is a high-intensity intermittent sport with large energy demands. In a repeated-measures design, we analysed the nutritional intake and training load of fourteen female football players (22.50 ± 4.38 y; 57.23 ± 8.61 kg; 164 ± 6.00 cm; 18.33 ± 2.48% of fat mass and 23.71 ± 2.51 kg of muscle mass) competing in the highest female Football Portuguese League across a typical mid-season microcycle. The microcycle had one match day (MD), one recovery session (two days after the MD, MD+2), three training sessions (MD-3, MD-2, MD-1) and two rest days (MD+1). Energy intake and CHO (g.kg.BW−1) intake were lower on the days before the competition (MD+2, MD-3, MD-2 and MD-1 vs. MD; p < 0.05; ES: 0.60−1.30). Total distance, distance covered at high-speed running (HSRD) and the high metabolic distance load (HMLD) were lower on MD+2, MD-3 and MD-1 compared with MD (p < 0.05; ES: <0.2−5.70). The internal training load was lower in all training sessions before the competition (MD+2, MD-3, MD-2 and MD-1 vs. MD; p ≤ 0.01; ES: 1.28−5.47). Despite the small sample size and a single assessment in time, the results suggest that caloric and CHO intake were below the recommendations and were not structured based on the physical requirements for training sessions or match days.

The Hamstrings: Anatomic and Physiologic Variations and Their Potential Relationships With Injury Risk.

The incidence and recurrence of hamstrings injuries are very high in sports, posing elevated performance and financial-related costs. Attempts to identify the risk factors involved in predicting vulnerability to hamstrings injury is important for designing exercise-based programs that aim to mitigate the rate and severity of hamstrings injuries and improve rehabilitation strategies. However, research has shown that non-modifiable risk factors may play a greater role than modifiable risk factors. Recognizing non-modifiable risk factors and understanding their implications will afford the prescription of better suited exercise programs, i.e., that are more respectful of the individual characteristics. In a nutshell, non-modifiable risk factors can still be acted upon, even if indirectly. In this context, an underexplored topic is how intra and inter- individual anatomic and physiologic variations in hamstrings (e.g., muscle bellies, fiber types, tendon length, aponeurosis width, attachment sites, sex- and age-related differences) concur to alter hamstrings injuries risk. Some anatomic and physiologic variations may be modifiable through exercise interventions (e.g., cross-sectional area), while others may not (e.g., supernumerary muscle bellies). This apparent dichotomy may hide a greater complexity, i.e., there may be risk factors that are partially modifiable. Therefore, we explored the available information on the anatomic variations of the hamstrings, providing a deeper insight into the individual risk factors for hamstrings injuries and contributing with better knowledge and potential applications toward a more individualized exercise prescription.

BDNF Impact on Biological Markers of Depression-Role of Physical Exercise and Training.

Depression is the most common and devastating psychiatric disorder in the world. Its symptoms, especially during the pandemic, are observed in all age groups. Exercise training (ET) is well known as a non-pharmacological strategy to alleviate clinical depression. The brain-derived neurotrophic factor (BDNF) is one of the biological factors whose expression and secretion are intensified in response to ET. BDNF is also secreted by contracted skeletal muscle that likely exerts para-, auto- and endocrine effects, supporting the crosstalk between skeletal muscle and other distant organs/tissues, such as the nervous system. This finding suggests that they communicate and work together to induce improvements on mood, cognition, and learning processes as BDNF is the main player in the neurogenesis, growth, and survival of neurons. Therefore, BDNF has been recognized as a therapeutic factor in clinical depression, especially in response to ET. The underlying mechanisms through which ET impacts depression are varied. The aim of this review was to provide information of the biological markers of depression such as monoamines, tryptophan, endocannabinoids, markers of inflammatory processes (oxidative stress and cytokines) stress and sex hormones and their relationship to BDNF. In addition, we reviewed the effects of ET on BNDF expression and how it impacts depression as well as the potential mechanisms mediating this process, providing a better understanding of underlying ET-related mechanisms in depression.

Strength Training to Prevent Falls in Older Adults: A Systematic Review with Meta-Analysis of Randomized Controlled Trials.

We performed a systematic review with meta-analysis of randomized controlled trials (RCTs) to assess the effects of strength training (ST), as compared to alternative multimodal or unimodal exercise programs, on the number of falls in older adults (≥60 years). Ten databases were consulted (CINAHL, Cochrane Library, EBSCO, EMBASE, PEDro, PubMed, Scielo, Scopus, SPORTDiscus and Web of Science), without limitations on language or publication date. Eligibility criteria were as follows: RCTs with humans ≥60 years of age of any gender with one group performing supervised ST and a group performing another type of exercise training, reporting data pertaining falls. Certainty of evidence was assessed with Grading of Recommendations, Assessment, Development and Evaluation (GRADE). Meta-analysis used a random effects model to calculate the risk ratio (RR) for number of falls. Five RCTs with six trials were included (n = 543, 76% women). There was no difference between ST and alternative exercise interventions for falls (RR = 1.00, 95% CI 0.77-1.30, p = 0.99). The certainty of evidence was very low. No dose-response relationship could be established. In sum, ST showed comparable RR based on number of falls in older adults when compared to other multimodal or unimodal exercise modalities, but evidence is scarce and heterogeneous, and additional research is required for more robust conclusions. Registration: PROSPERO CRD42020222908.

Skeletal Muscle-Adipose Tissue-Tumor Axis: Molecular Mechanisms Linking Exercise Training in Prostate Cancer.

Increased visceral adiposity may influence the development of prostate cancer (PCa) aggressive tumors and cancer mortality. White adipose tissue (WAT), usually referred to as periprostatic adipose tissue (PPAT), surrounds the prostatic gland and has emerged as a potential mediator of the tumor microenvironment. Exercise training (ET) induces several adaptations in both skeletal muscle and WAT. Some of these effects are mediated by ET-induced synthesis and secretion of several proteins, known as myo- and adipokines. Together, myokines and adipokines may act in an endocrine-like manner to favor communication between skeletal muscle and WAT, as they may work together to improve whole-body metabolic health. This crosstalk may constitute a potential mechanism by which ET exerts its beneficial role in the prevention and treatment of PCa-related disorders; however, this has not yet been explored. Therefore, we reviewed the current evidence on the effects of skeletal muscle-WAT-tumor crosstalk in PCa, and the potential mediators of this process to provide a better understanding of underlying ET-related mechanisms in cancer.

Bidirectional Interactions between the Menstrual Cycle, Exercise Training, and Macronutrient Intake in Women: A Review.

Women have a number of specificities that differentiate them from men. In particular, the role of sex steroid hormones and the menstrual cycle (MC) significantly impact women's physiology. The literature has shown nonlinear relationships between MC, exercise, and nutritional intake. Notably, these relationships are bidirectional and less straightforward than one would suppose. For example, the theoretical implications of the MC's phases on exercise performance do not always translate into relevant practical effects. There is often a disconnect between internal measures (e.g., levels of hormone concentrations) and external performance. Furthermore, it is not entirely clear how nutritional intake varies across the MC's phases and whether these variations impact on exercise performance. Therefore, a thorough review of the existing knowledge could help in framing these complex relationships and potentially contribute to the optimization of exercise prescription and nutritional intake according to the naturally occurring phases of the MC. Throughout this review, an emerging trend is the lack of generalizability and the need to individualize interventions, since the consequences of the MC's phases and their relationships with exercise and nutritional intake seem to vary greatly from person to person. In this sense, average data are probably not relevant and could potentially be misleading.

Self-Paced Free-Running Wheel Mimics High-Intensity Interval Training Impact on Rats' Functional, Physiological, Biochemical, and Morphological Features.

Free-running wheel (FRW) is an animal exercise model that relies on high-intensity interval moments interspersed with low-intensity or pauses apparently similar to those performed in high-intensity interval training (HIIT). Therefore, this study, conducted over a 12-weeks period, aimed to compare functional, thermographic, biochemical and morphological skeletal and cardiac muscle adaptations induced by FRW and HIIT. Twenty-four male Wistar rats were assigned into three groups: sedentary rats (SED), rats that voluntarily exercise in free wheels (FRW) and rats submitted to a daily HIIT. Functional tests revealed that compared to SED both FRW and HIIT increased the ability to perform maximal workload tests (MWT-cm/s) (45 ± 1 vs. 55 ± 2 and vs. 65 ± 2). Regarding thermographic assays, FRW and HIIT increased the ability to lose heat through the tail during MWT. Histochemical analyzes performed in tibialis anterior (TA) and soleus (SOL) muscles showed a general adaptation toward a more oxidative phenotype in both FRW and HIIT. Exercise increased the percentage of fast oxidative glycolytic (FOG) in medial fields of TA (29.7 ± 2.3 vs. 44.9 ± 4.4 and vs. 45.2 ± 5.3) and slow oxidative (SO) in SOL (73.4 ± 5.7 vs. 99.5 ± 0.5 and vs. 96.4 ± 1.2). HITT decreased fiber cross-sectional area (FCSA-µm2) of SO (4350 ± 286.9 vs. 4893 ± 325 and vs. 3621 ± 237.3) in SOL. Fast glycolytic fibers were bigger across all the TA muscle in FRW and HIIT groups. The FCSA decrease in FOG fibers was accompanied by a circularity decrease of SO from SOL fibers (0.840 ± 0.005 vs. 0.783 ± 0.016 and vs. 0.788 ± 0.010), and a fiber and global field capillarization increase in both FRW and HIIT protocols. Moreover, FRW and HIIT animals exhibited increased cardiac mitochondrial respiratory control ratio with complex I-driven substrates (3.89 ± 0.14 vs. 5.20 ± 0.25 and vs. 5.42 ± 0.37). Data suggest that FRW induces significant functional, physiological, and biochemical adaptations similar to those obtained under an intermittent forced exercise regimen, such as HIIT.

Peripherally administered melanocortins induce mice fat browning and prevent obesity.

BACKGROUND/OBJECTIVES: The browning of white adipose tissue (WAT) has been in the spotlight during the last years, becoming an attractive approach to combat obesity. Melanocortin neuropeptides, such as α-melanocyte-stimulating hormone (α-MSH), are well-known regulators of appetite at the central nervous system, but its role in adipocyte metabolism is poorly elucidated. This study sought to verify if α-MSH can induce transdifferentiation of white to brown/beige adipocytes and to determine whether it can ameliorate the obesity phenotype. METHODS: The browning effect of α-MSH was determined in isolated adipocytes using the 3T3-L1 cell line and in inguinal subcutaneous adipose tissue (ingWAT) of diet-induced obese (DIO) mice by quantifying the expression of browning hallmark genes, oxygen consumption, and mitochondrial biogenesis. α-MSH protection from diet-induced obesity was evaluated by analyzing mice body weight, fat mass, and lipid and glucose serum profiles. RESULTS: Here, we report that α-MSH activates a thermogenic gene program and increases the mitochondrial respiratory rate in 3T3-L1 adipocytes and ingWAT of DIO mice. Without affecting food intake, peripheral administration of α-MSH decreases body weight and ingWAT mass, promoting a significant rise in the number of smaller adipocytes, whereas it lowered the larger ones. Additionally, there was an increase in the mass of brown adipose tissue. Browning activation occurs concomitantly with improvement on serum lipid profile, insulin resistance, and glucose homeostasis. CONCLUSIONS: This study highlights the anti-obesity properties of melanocortins by promoting ingWAT browning and provides new perspectives for future designing of more effective therapeutic strategies.

Association Between Somatotype Profile and Health-Related Physical Fitness in Special Police Unit.

OBJECTIVES: To characterize somatotype profile and analyze the association between somatotype components, physical, and physiological variables in special police unit (SPU) officers. METHODS: One hundred eight male SPU officers, aged 42.5 ±â€Š4.1 years. Somatotype profile, predicted maximal oxygen consumption (VO2max), and physical performance tests were evaluated. RESULTS: The mean somatotypes were 4.04-6.38-1.22. All values clustered amongst the endo-mesomorphism (86%) while mesomorphy was the dominant component (98%). The mean of predicted VO2max was 50.3 ±â€Š5.2 mL kg min. The body mass index (BMI) is more than or equal to 30 was associated to a lowest predicted VO2max (r = 0.613). The VO2max negatively correlated with mesomorphy (r = -0.251). Mesomorphy somatotype was positively associated with maximal and explosive strength tests. CONCLUSION: Our findings indicated that somatotype profile can be used as an accurate method to assess body physique and shape in SPU officers and an ecto-mesomorphism profile was associated to superior performance in physical and physiological measures.

Physical exercise mitigates high-fat diet-induced adiposopathy and related endocrine alterations in an animal model of obesity

The dysregulation of adipokine secretion owing to adiposopathy can contribute to the pathogenesis of obesity-related disorders. Being that exercise is an advised strategy against obesity-induced adiposopathy, we aimed to analyze the role of physical exercise as a preventive and therapeutic strategy against high-fat diet (HFD)-induced adipokine and ghrelin alterations. Rats were pair-fed the Lieber De Carli standard diet (S, 35 Kcal% fat) or HFD (71 Kcal% fat) over 17 weeks. Animals were assigned into four groups as follows: standard diet sedentary (SS), standard diet voluntary physical activity (SVPA), high-fat diet sedentary (HS), and high-fat diet voluntary physical activity (HVPA). After 9 weeks of dietary treatment, half of the SS and HS animals were submitted to an 8-week endurance training program, standard diet endurance training (SET), and high-fat-diet endurance training (HET) groups, maintaining the respective diets. Although there were no changes in body weight, HFD increased visceral adiposity, percentage of large adipocytes, hypoxia inducible factor (HIF)-1α, and leptin contents in epididymal adipose tissue (eWAT) and decreased plasma content of adiponectin (AdipQ). Both VPA and ET decreased visceral adiposity and percentage of large adipocytes in HFD-fed animals, but ET also increased the percentage of small- to medium-sized adipocytes. VPA increased plasma growth hormone secretagogue receptor (GHS-R) and decreased leptin protein in HVPA group. ET decreased plasma insulin and leptin levels and eWAT HIF-1α and leptin expression in HET group. Moreover, ET improved insulin sensitivity, plasma high molecular weight, and AdipQ and ghrelin levels and increased eWAT and GHS-R expression. Our data suggest that exercise, particularly ET, reverted adiposopathy and related endocrine alterations induced by an isocaloric HFD pair-fed diet

Physical exercise mitigates high-fat diet-induced adiposopathy and related endocrine alterations in an animal model of obesity.

The dysregulation of adipokine secretion owing to adiposopathy can contribute to the pathogenesis of obesity-related disorders. Being that exercise is an advised strategy against obesity-induced adiposopathy, we aimed to analyze the role of physical exercise as a preventive and therapeutic strategy against high-fat diet (HFD)-induced adipokine and ghrelin alterations. Rats were pair-fed the Lieber De Carli standard diet (S, 35 Kcal% fat) or HFD (71 Kcal% fat) over 17 weeks. Animals were assigned into four groups as follows: standard diet sedentary (SS), standard diet voluntary physical activity (SVPA), high-fat diet sedentary (HS), and high-fat diet voluntary physical activity (HVPA). After 9 weeks of dietary treatment, half of the SS and HS animals were submitted to an 8-week endurance training program, standard diet endurance training (SET), and high-fat-diet endurance training (HET) groups, maintaining the respective diets. Although there were no changes in body weight, HFD increased visceral adiposity, percentage of large adipocytes, hypoxia inducible factor (HIF)-1α, and leptin contents in epididymal adipose tissue (eWAT) and decreased plasma content of adiponectin (AdipQ). Both VPA and ET decreased visceral adiposity and percentage of large adipocytes in HFD-fed animals, but ET also increased the percentage of small- to medium-sized adipocytes. VPA increased plasma growth hormone secretagogue receptor (GHS-R) and decreased leptin protein in HVPA group. ET decreased plasma insulin and leptin levels and eWAT HIF-1α and leptin expression in HET group. Moreover, ET improved insulin sensitivity, plasma high molecular weight, and AdipQ and ghrelin levels and increased eWAT and GHS-R expression. Our data suggest that exercise, particularly ET, reverted adiposopathy and related endocrine alterations induced by an isocaloric HFD pair-fed diet.

Effects of endurance training on autophagy and apoptotic signaling in visceral adipose tissue of prolonged high fat diet-fed rats.

PURPOSE: Autophagy and apoptosis play critical roles in both development and tissue homeostasis in response to (patho)physiological stimuli, such as high-fat diet (HFD) and endurance training (ET). Therefore, we aimed to investigate how ET modulates autophagy and apoptotic-related signaling in visceral adipose tissue of long-standing HFD-fed rats. METHODS: The study was conducted over a 17-week period on Sprague-Dawley rats, which were divided into four groups (n = 8/group): standard diet sedentary (STD+SED), high-fat diet sedentary (HFD+SED), standard diet ET (STD+ET) and high-fat diet ET (HFD+ET). After 9 weeks of dietary regimens, ET groups were trained for 8 weeks on treadmill (5 days/week at 25 m/min for 60 min/day), while maintaining dietary regimens. Autophagy and apoptotic-signaling markers in epididymal white adipose tissue (eWAT) were determined using RT-qPCR, Western blot and spectrometry techniques. RESULTS: ET reduced body weight, visceral fat mass and HOMA-IR in standard and HF diet-fed animals. Moreover, ET reverted the HFD-induced increases in the percentage of larger adipocytes and also reduced the percentage of smaller adipocytes. The HFD decreased pre-adipocyte factor 1 (DLK1/PREF1) and increased the pro-apoptotic markers (Bax protein and caspase 3-like activity), while having no impact on autophagy markers. However, ET increased DLK1/PREF1 and Bcl-2 in both diet types, while decreasing Bax and caspases 9, 8 and 3-like activities in HFD feeding rats. Additionally, Beclin-1 and p62 protein significantly increased in ET groups of both diet types. CONCLUSIONS: Data demonstrate that 8 weeks of ET was effective in attenuating apoptotic-related signaling in long-standing HFD-fed rats. Moreover, HFD and ET had no impact on VAT autophagy markers.

Can exercise training counteract doxorubicin-induced oxidative damage of testis proteome?

The use of the chemotherapeutic drug doxorubicin (DOX) is limited by its toxicity in several organs such as testes. So, we analyzed the effect of endurance treadmill exercise training (EX) performed before sub-chronic DOX treatment on sperm count and motility, testes markers of oxidative damage and apoptosis. Tissue profiling of proteins more susceptible to oxidation was made to identify the molecular pathways regulated by oxidative modifications, as nitration and carbonylation. Twenty-four adult male rats were divided into four groups (n=6/group): sedentary saline (SED+SAL), sedentary sub-chronically injected with DOX (2mg-kg-1 per week, during 7 weeks; SED+DOX), 12 weeks trained saline (EX+SAL) and trained treated with DOX (EX+DOX). DOX treatment started 5 weeks after the beginning of the exercise program. Testes caspase-3, -8 and -9, as well as aconitase activities, the content of malondialdehyde (MDA), sulfhydryl groups (-SH), carbonyl and nitrotyrosine derivatives were determined. Modified proteins were identified by 2D-Western blot followed by MALDI-TOF/TOF mass spectrometry, and bioinformatic analysis was performed to assess the biological processes regulated by these chemical modifications. The decreased sperm motility induced by DOX was not modified by exercise. Significant increases in MDA content in SED+DOX and in caspase-3 and -9 activities in EX+DOX were found. Despite no significant differences in the levels of carbonylated and nitrated proteins, exercise modulated testis proteome susceptibility to oxidation in DOX-treated group, with less modified proteins identified. Zinc finger Ran-binding domain-containing protein 2 (ZRAB2) and AN1-type zinc finger protein 3 (ZFAN3) were among the proteins found oxidativelly modified. Although no marked alterations in testes oxidative damage were noticed, proteomic analysis of oxidativelly modified proteins highlighted the protective role of exercise against oxidative damage of some proteins involved in metabolism and stress response against DOX.

Impact of physical exercise on visceral adipose tissue fatty acid profile and inflammation in response to a high-fat diet regimen.

PURPOSE: Studies associate specific fatty-acids (FA) with the pathophysiology of inflammation. We aimed to analyze the impact of exercise on adipose tissue FA profile in response to a high-fat diet (HFD) and to ascertain whether these exercise-induced changes in specific FA have repercussions on obesity-related inflammation. METHODS: Sprague-Dawley rats were assigned into sedentary, voluntary physical-activity (VPA) and endurance training (ET) groups fed a standard (S, 35kcal% fat) or high-fat (71kcal% fat) diets. VPA-animals had unrestricted access to wheel-running. After 9-wks, ET-animals engaged a running protocol for 8-wks, while maintained dietary treatments. The FA content in epididymal white-adipose tissue (eWAT) triglycerides was analyzed by gas-chromatography and the expression of inflammatory markers was determined using RT-qPCR, Western and slot blotting. RESULTS: Eight-wks of ET reversed obesity-related anatomical features. HFD increased plasma tumor necrosis factor (TNF)-α content and eWAT monocyte chemoattractant protein (MCP)-1 protein expression. HFD decreased eWAT content of saturated FA and monounsaturated FA, while increased linoleic acid and prostaglandin E2 (PGE2) levels in eWAT. VPA decreased visceral adiposity, adipocyte size and MCP-1 in HFD-fed animals. The VPA and ET interventions diminished palmitoleic acid and increased linoleic acid in HFD-fed groups. Moreover, both interventions increased PGE2 levels in standard diet-fed groups and decreased in HFD. ET increased eWAT fatty acid desaturase 1 (FADS1) and elongase 5 (ELOVL5) protein content in both diet types. ET reduced eWAT inflammatory markers (TNF-α, IL-6), macrophage recruitment (MCP-1 and F4/80) and increased IL-10/TNF-α ratio in plasma and in eWAT in both diet types. CONCLUSIONS: Exercise induced FA-specific changes independently of dietary FA composition, but only ET attenuated the inflammatory response in VAT of HFD-fed rats. Moreover, the exercise-induced FA changes did not correlate with the inflammatory response in VAT of rats submitted to HFD.

Xanthohumol and 8-prenylnaringenin ameliorate diabetic-related metabolic dysfunctions in mice.

Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by metabolic disturbances in specific tissues. The present work aimed to analyze the effects of xanthohumol (XN) and 8-prenylnaringenin (8PN), two beer-derived polyphenols, in liver and skeletal muscle lipid and glycolytic metabolism in T2DM mice model. Thirty C57Bl/6 mice were randomly divided into five groups: standard diet (control), high-fat diet (DM), high-fat diet plus ethanol (DM-Ethanol), high-fat diet plus 10 mg/L XN (DM-XN) and high-fat diet plus 10 mg/L 8PN (DM-8PN) during 20 weeks. Fasting blood glucose and insulin tolerance tests were performed 1 week before sacrifice. At the end of the study, blood, liver and skeletal muscle were collected. Both XN and 8PN treatments prevented body weight gain; decreased glycemia, triglyceride, cholesterol and alkaline phosphatase levels; and improved insulin sensitivity. Polyphenols promoted hepatic and skeletal muscle AMP-activated protein kinase (AMPK) activation, diminishing the expression of target lipogenic enzymes (sterol regulatory element binding protein-1c and fatty acid synthase) and acetyl-CoA carboxylase activity. Moreover, both XN and 8PN treatments decreased VEGFR-1/VEGFB pathway, involved in fatty acid uptake, and increased AS160 expression, involved in GLUT4 membrane translocation. Presented data demonstrated that both XN and 8PN treatment resulted in AMPK signaling pathway activation, thus suppressing lipogenesis. Their consumption prevented body weight gain and improved plasma lipid profile, with significant improvement of insulin resistance and glucose tolerance. XN- or 8PN-enriched diet could ameliorate diabetic-associated metabolic disturbances by regulating glucose and lipid pathways.