Search

Funding information: PEst‐OE/SAU/UI0038/2014 to Department of Biochemistry (U38/FCT) of Faculty of Medicine, Grant/Award Number: FCT grant; PEst‐OE/SAU/UI0617/2011 and PTDC/DTP‐DES/7087/2014‐POCI‐01‐0145‐FEDER‐ 016690 to CIAFEL, Grant/Award Number: FCT Grant; SFRH/BDE/33798/2009 to CP, Grant/Award Number: FCT grant; SFRH/BD/71149/2010 to EP, Grant/Award Number: FCT grant Obesity is a predictive factor for the development of nonalcoholic steatohepatitis (NASH). Although some of the mechanisms associated with NASH development are still elusive, its pathogenesis relies on a complex broad spectrum of (interconnected) metabolic-based disorders. We analyzed the effects of voluntary physical activity (VPA) and endurance training (ET), as preventive and therapeutic nonpharmacological strategies, respectively, against hepatic endoplasmic reticulum (ER) stress, ER-related proapoptotic signaling, and oxidative stress in an animal model of high-fat diet (HFD)-induced NASH. Adult male Sprague-Dawley rats were divided into standard control liquid diet (SCLD) or HFD groups, with sedentary, VPA, and ET subgroups in both (sedentary animals with access to SCLD [SS], voluntarily physically active animals with access to SCLD [SV], and endurance-trained animals with access to SCLD [ST] in the former and sedentary animals with access to liquid HFD [HS], voluntarily physically active animals with access to liquid HFD [HV], and endurance-trained animals with access to liquid HFD [HT] in the latter, respectively). Hepatic ER stress and ER-related proapoptotic signaling were evaluated by Western blot and reverse transcriptase-polymerase chain reaction; redox status was evaluated through quantification of lipid peroxidation, protein carbonyls groups, and glutathione levels as well as antioxidant enzymes activity. In SCLD-treated animals, VPA significantly decreased eukaryotic initiation factor-2 alpha (eIF2α). In HFD-treated animals, VPA significantly decreased eIF2α and phospho-inositol requiring enzyme-1 alpha (IRE1α) but ET significantly decreased eIF2α and significantly increased both spliced X-box binding protein 1 (sXBP1) and unspliced X-box binding protein 1; a significant increase of phosphorylated-eIF2α (p-eIF2α) to eIF2α ratio occurred in ET versus VPA. HS compared to SS disclosed a significant increase of total and reduced glutathione, HV compared to SV a significant increase of oxidized glutathione, HT compared to ST a significant increase of p-eIF2α to eIF2α ratio and sXBP1. Physical exercise counteracts NASH-related ER stress and its associated deleterious consequences through a positive and dynamical modulation of the hepatic IRE1α-X-box binding protein 1 pathway. info:eu-repo/semantics/publishedVersion

New findings What is the central question of this study? To what extent does testosterone influence hemoglobin formation during male puberty? What is the main finding and its importance? In boys, testosterone might be responsible for about 65% of the increase in hemoglobin mass during puberty. The underlying mechanisms are assumed to be twofold: (i) indirectly, mediated by the increase in LBM, and (ii) directly by immediate testosterone effects on erythropoiesis. Thereby, an increase in testosterone by 1ng/ml is associated with an increase in Hbmass by ∼65g. These processes are likely to determine endurance performance in adulthood. Abstract The amount of hemoglobin during puberty is related to endurance performance in adulthood. During male puberty, testosterone stimulates erythropoiesis and could therefore be used as a marker for later endurance performance. This cross-sectional study aimed to determine the relationship between serum testosterone concentration and hemoglobin mass (Hbmass) in both male and female children and adolescents and to evaluate the possible influences of altitude and training. Three-hundred thirteen differently trained boys and girls aged from 9 to 18 years and living at altitudes of 1000m and 2600m above sea level entered the study. The stage of sexual maturation was determined according to the classification of Tanner. Testosterone was measured by ELISA. Hbmass was determined by CO-rebreathing. Hemoglobin concentration did not change during maturation in girls and was 11% higher during puberty in boys, while Hbmass was elevated by 33% in Tanner stage V compared to stage II in girls (373±88g vs 498±77g) and by 95% in boys, (428±95g vs 832±143g) respectively. This difference can most likely be attributed to indirect testosterone influences through an increase in LBM and to direct testosterone effects on erythropoiesis, which increase the Hbmass by ∼65g per 1ng/ml. Altitude and training statuses were not associated with testosterone, but with an increase in Hbmass (altitude by 1.1g/kgLBM, training by 0.8 g/kgLBM). Changes in Hbmass are closely related to testosterone levels during male puberty. Further studies will show whether testosterone and Hbmass during childhood and adolescence can be used as diagnostic tools for endurance talents. This article is protected by copyright. All rights reserved.

This study aimed at examining the suitability of a standard treadmill test (TT), popular intermittent field tests, and small-sided football matches to induce maximal heart rate (HRmax ) in recreational football players. Sixty-six inactive untrained male subjects (age: 39.3 ± 5.8 years, VO2max : 41.2 ± 6.2 mL kg-1 min-1 , body mass: 81.9 ± 10.8 kg, height: 173.2 ± 6.4 cm) were evaluated. On separate occasions, the players were randomly submitted to a progressive VO2max TT, to the Yo-Yo intermittent endurance level 1 (YYIE1) and level 2 (YYIE2) tests, to the Yo-Yo intermittent recovery level 1 (YYIR1) test, and to 7v7 (43 × 27 m pitch, 83 m2 /player) football matches (45 minutes; 2-4 matches/player). To ensure data consistency, exercise HR was recorded using the same HR monitors in all the experimental conditions. A total of 73%, 24%, 18%, 17%, and 30% of the players achieved their HRmax during the YYIE1, YYIE2, YYIR1, TT, and the small-sided football matches, respectively. The probability of achieving HRmax increased proportionally to test duration, with 7.8 minutes as the cutoff time. Variations in HRpeak of ±2 b min-1 should be regarded as of practical relevance. YYIE1 HRpeak provided the most accurate estimation of a subject's individual HRmax and much higher probability of reaching HRmax . Nevertheless, the results of this study suggest caution in considering a reference test for HRmax assessment in this population. The use of confirmation tests is still highly advisable when the test duration is shorter than 7.8 minutes. In this regard, field tests seem to be suitable and accurate for individual HRmax assessment in recreational football players.

SPECIAL ISSUE: 'FOIEGRAS-Bioenergetic Remodelling in the Pathophysiology and Treatment of Non-Alcoholic Fatty Liver Disease'. Background Non-alcoholic fatty liver disease (NAFLD) emerges as significant health burden worldwide. Lifestyle changes, unhealthy dietary habits and physical inactivity, can trigger NAFLD development. Persisting on these habits during pregnancy affects in utero environment and prompts a specific metabolic response in foetus resulting in offspring metabolic maladjustments potentially critical for developing NAFLD later in life. The increasing prevalence of NAFLD, particularly in children, has shifted the research focus towards preventive and therapeutic strategies. Yet, designing effective approaches that can break the NAFLD intergenerational cycle becomes even more complicated. Regular physical exercise (PE) is a powerful non-pharmacological strategy known to counteract deleterious metabolic outcomes. In this narrative review, we aimed to briefly describe NAFLD pathogenesis focusing on maternal nutritional challenge and foetal programming, and to provide potential mechanisms behind the putative intergenerational effect of PE against metabolic diseases, including liver diseases. Methods Following detailed electronic database search, recent existing evidence about NAFLD development, intergenerational programming and gestational exercise effects was critically analysed and discussed. Results PE during pregnancy could have a great potential to counteract intergenerational transmission of metabolic burden. The interplay between different PE roles-metabolic, endocrine and epigenetic-could offer a more stable in utero environment to the foetus, thus rescuing offspring vulnerability to metabolic disturbances. Conclusions The better understanding of maternal PE beneficial consequences on offspring metabolism could reinforce the importance of PE during pregnancy as an indispensable strategy in improving offspring health.

'Special issue - In Utero and Early Life Programming of Aging and Disease'. Skeletal muscle (SM) adaptations to physical exercise (PE) have been extensively studied due, not only to the relevance of its in situ plasticity, but also to the SM endocrine-like effects in noncontractile tissues, such as brain, liver or adipocytes. Regular PE has been considered a pleiotropic nonpharmacological strategy to prevent and counteract the deleterious consequences of several metabolic, cardiovascular, oncological and neurodegenerative disorders. Additionally, PE performed by parents seems to have a direct impact in the offspring through the transgenerational programming of different tissues, such as SM. In fact, SM offspring programming mechanisms seems to be orchestrated, at least in part, by epigenetic machinery conditioning transcriptional or post-transcriptional processes. Ultimately, PE performed in the early in life is also a critical window of opportunity to positively modulate the juvenile and adult phenotype. Parental PE has a positive impact in several health-related offspring outcomes, such as SM metabolism, differentiation, morphology and ultimately in offspring exercise volition and endurance. Also, early-life PE counteracts conceptional-related adverse effects and induces long-lasting healthy benefits throughout adulthood. Additionally, epigenetics mechanisms seem to play a key role in the PE-induced SM adaptations. Despite the undoubtedly positive role of parental and early-life PE on SM phenotype, a strong research effort is still needed to better understand the mechanisms that positively regulate PE-induced SM programming.

We aimed to investigate the effects of two physical exercise models, voluntary physical activity (VPA) and endurance training (ET) as preventive and therapeutic strategies, respectively, on lipid accumulation regulators and mitochondrial content in VAT of rats fed a high-fat diet (HFD). Sprague-Dawley rats (6 weeks old, n=60) were assigned into sedentary and VPA groups fed isoenergetic diets: standard (S, 35 kcal% fat) or HFD (71 kcal% fat). The VPA groups had free access to wheel running during the entire protocol. After 9 weeks, half of the sedentary animals were exercised on a treadmill while maintaining the dietary treatments. The HFD induced no changes in plasma non-esterified fatty acids (NEFA) and glycerol levels and decreased oxidative phosphorylation (OXPHOS) subunit IV and increased truncated/full-length sterol regulatory element-binding transcription factor 1c (SREBP1c) ratio in epididymal white adipose tissue (eWAT). VPA decreased plasma glycerol levels, aquaglyceroporin 7 (AQP7) and increased subunit I of cytochrome c oxidase (COX) protein, in standard diet fed animals. Eight weeks of ET decreased body weight, visceral adiposity and adipocyte size and plasma NEFA and glycerol levels, as well as AQP7 protein expression in eWAT. ET increased fatty acid translocase (FAT/CD36), mitochondrial content of complexes IV and V subunits, mitochondrial biogenesis and dynamic (mitofusins and optic atrophy 1)-related proteins. Moreover, lipogenesis-related markers (SREBP1c and acetyl CoA carboxylase) were reduced after 8 weeks of ET. In conclusion, ET-induced alterations reflect a positive effect on mitochondrial function and the overall VAT metabolism of HFD-induced obese rats.

Exercise is one of the most effective strategies to maintain a healthy body and mind, with particular beneficial effects of exercise on promoting brain plasticity, increasing cognition and reducing the risk of cognitive decline and dementia in later life. Moreover, the beneficial effects resulting from increased physical activity occur at different levels of cellular organization, mitochondria being preferential target organelles. The relevance of this review article relies on the need to integrate the current knowledge of proposed mechanisms, focus mitochondria, to explain the protective effects of exercise that might underlie neuroplasticity and seeks to synthesize these data in the context of exploring exercise as a feasible intervention to delay cognitive impairment associated with neurodegenerative conditions, particularly Alzheimer disease.

Eur J Clin Invest 2010; 40 (4): 319–329 Abstract Background Hyperglycaemia-resulting in mitochondrial bioenergetics’ complications is associated with skeletal muscle dysfunction. The aim of this work was to analyse the effect of long-term severe hyperglycaemia on gastrocnemius mitochondrial bioenergetics, with special relevance on the susceptibility to mitochondrial permeability transition pore (MPTP) opening. Methods Sixteen adult (6- to 8-week-old) male Wistar rats were randomly divided into two groups (n = 8/group): control and diabetic. A single dose (50 mg kg−1) of streptozotocin (STZ) was administrated i.p. to induce hyperglycaemia. In vitro mitochondrial oxygen consumption rates, membrane potential (Δψ) fluctuations, MPTP induction as followed by osmotic swelling and extramitochondrial calcium movements and caspase 9-like activity were evaluated 18 weeks after STZ treatment. Results STZ treatment induced an increase in state 4 and a decrease in the respiratory control ratio with complex I substrates (P