1. Initial glutathione depletion during short-term bed rest : pinpointing synthesis and degradation checkpoints in the γ-glutamyl cycleFilippo Giorgio Di Girolamo, Filippo Mearelli, Mariella Sturma, Nicola Fiotti, Kaja Teraž, Alja Ivetac, Alessio Nunnari, Pierandrea Vinci, Boštjan Šimunič, Rado Pišot, Gianni Biolo, 2024, izvirni znanstveni članek Povzetek: Hypokinesia triggers oxidative stress and accelerates the turnover of the glutathione system via the γ-glutamyl cycle. Our study aimed to identify the regulatory checkpoints controlling intracellular glutathione levels. We measured the intermediate substrates of the γ-glutamyl cycle in erythrocytes from 19 healthy young male volunteers before and during a 10-day experimental bed rest. Additionally, we tracked changes in glutathione levels and specific metabolite ratios up to 21 days of bed rest. Using gas chromatography-mass spectrometry and the internal standard technique, we observed a 9 ± 9% decrease in glutathione levels during the first 5 days of bed rest, followed by an 11 ± 9% increase from the 5th to the 10th day, nearly returning to baseline ambulatory levels. The cysteinyl-glycine-to-glutathione ratio, reflecting γ-glutamyl cyclotransferase activity (a key enzyme in glutathione breakdown), rose by 14 ± 22% in the first 5 days and then fell by 10 ± 14% over the subsequent 5 days, again approaching baseline levels. Additionally, the γ-glutamyl cysteine-to-cysteine ratio, indicative of γ-glutamyl cysteine synthetase activity (crucial for glutathione synthesis), increased by 12 ± 30% on day 5 and by 29 ± 41% on day 10 of bed rest. The results observed on day 21 of bed rest confirm those seen on day 10. By calculating the ratio of product concentration to precursor concentration, we assessed the efficiency of these key enzymes in glutathione turnover. These results were corroborated by directly measuring glutathione synthesis and degradation rates in vivo using stable isotope techniques. Our findings reveal significant changes in glutathione kinetics during the initial days of bed rest and identify potential therapeutic targets for maintaining glutathione levels.
Ključne besede: antioxidant, muscle unloading, glutathion turnover, γ-glutamyl cycle, gamma-glutamyl cycle
Objavljeno v DiRROS: 21.11.2024; Ogledov: 116; Prenosov: 1102
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2. The abdominal adiposity index (a body shape index) predicts 10-year all-cause mortality in elderly active non-obese subjectsAlessio Nunnari, Filippo Giorgio Di Girolamo, Kaja Teraž, Nicola Fiotti, Boštjan Šimunič, Filippo Mearelli, Rado Pišot, Gianni Biolo, 2024, izvirni znanstveni članek Povzetek: Background/Objectives: A Body Shape Index (ABSI), which accounts for waist circumference relative to mass and height, shows a robust association with mortality risk. The present study evaluates the effectiveness of ABSI as a predictor of 10-year all-cause mortality in physically active, non-obese elderly individuals. Methods: This prospective cohort study included 159 volunteers (94 women, aged 60–80 years), recruited in the frame of the “Physical Activity and Nutrition for Great Ageing” (PANGeA) Cross-border Cooperation Program Slovenia–Italy 2007–2013, and followed for 10 years. Baseline characteristics included anthropometric measurements, bioelectrical impedance analysis, and cardiovascular fitness tests (VO2max). Statistical analyses (Cox regression, Kaplan–Meier survival) were conducted to examine the relationship between ABSI and mortality. Results: During the 10-year follow-up, 10 deaths (6.7%) were recorded. ABSI (adjusted for age, smoking, comorbidities, and therapy) was an independent predictor of mortality (hazard ratio = 4.65, p < 0.001). Higher ABSI scores were linked to reduced VO2max (r = −0.190, p = 0.017) and increased systolic blood pressure (r = 0.262, p = 0.001). An ABSI-based predictive model showed strong discriminatory power (AUROC = 0.91). Conclusions: ABSI is a reliable predictor of 10-year mortality in active, non-obese elderly individuals and may improve risk stratification in clinical practice.
Ključne besede: ABSI, a body shape index, body shape, fre fat mass, sarcopenia, prognostic index, elderly, mortality
Objavljeno v DiRROS: 16.10.2024; Ogledov: 173; Prenosov: 296
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3. Metabolic consequences of anabolic steroids, insulin, and growth hormone abuse in recreational bodybuilders : implications for the world anti-doping agency passportFilippo Giorgio Di Girolamo, Chiara Biasinutto, Alessandro Mangogna, Nicola Fiotti, Pierandrea Vinci, Rado Pišot, Filippo Mearelli, Boštjan Šimunič, Chiara Roni, Gianni Biolo, 2024, izvirni znanstveni članek Povzetek: Background Hormonal doping in recreational sports is a public-health concern. The World Anti-Doping Agency (WADA) promoted the creation of the Athlete Biological Passport, aiming to monitor athlete’s biological variables over time to facilitate indirect detection of doping. Detection tests for anabolic androgenic steroids (AAS) and growth hormone (GH) are available while insulin abuse cannot be revealed. We have determined in recreational bodybuilders the metabolic effects associated with different patterns of hormone abuse. All analyses were conducted using Statistical Package for Social Sciences (SPSS) 21.0 software (SPSS Chicago, IL). Results We have assessed plasma concentrations of selected metabolic markers and fatty acid content in erythrocyte membranes of 92 male bodybuilders and in 45 healthy controls. Hormonal abuse was identified by anonymous questionnaires. 43% (%) of recruited bodybuilders regularly abused hormones, i.e., anabolic androgenic steroids (95%) often associated with GH (30%) and/or insulin (38%). HDL-cholesterol was lower in insulin and/or GH abusers. Alanine (ALT) and aspartic (AST) transaminases were greater in hormone abusing bodybuilders than in non-doping bodybuilders and controls. Insulin doping was selectively associated with increased plasma ALT-to-AST ratio. In erythrocyte membranes, elongase activity (i.e., stearic-to-palmitic ratio) was lower in insulin and/or growth hormone doping, whereas increased Δ-9 desaturase activity (i.e., palmitoleic-to-palmitic ratio) was selectively associated with insulin doping. Conclusions In conclusion, our study demonstrates that insulin and GH abuse are characterized by multiple alterations of specific metabolic markers. Although further studies are needed to test whether longitudinal monitoring of selected metabolic marker such as muscle contraction time, HDL levels, ALT-AST ratio as well as the activities of selected enzymes (e.g. Δ-9 desaturase and elongase), could contribute to the detection of insulin and GH abuse in sport.
Ključne besede: bodybuilders, doping, drug abuse, matabolism
Objavljeno v DiRROS: 03.04.2024; Ogledov: 556; Prenosov: 217
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4. Sarcopenia parameters in active older adults – an eight-year longitudinal studyKaja Teraž, Uroš Marušič, Miloš Kalc, Boštjan Šimunič, Primož Pori, Bruno Grassi, Stefano Lazzer, Marco Vicenzo Narici, Mojca Gabrijelčič Blenkuš, Pietro Enrico Di Prampero, Carlo Reggiani, Angelina Passaro, Gianni Biolo, Mladen Gasparini, Rado Pišot, 2023, izvirni znanstveni članek Povzetek: Background Sarcopenia is a common skeletal muscle syndrome that is common in older adults but can be mitigated by adequate and regular physical activity. The development and severity of sarcopenia is favored by several factors, the most influential of which are a sedentary lifestyle and physical inactivity. The aim of this observational longitudinal cohort study was to evaluate changes in sarcopenia parameters, based on the EWGSOP2 definition in a population of active older adults after eight years. It was hypothesized that selected active older adults would perform better on sarcopenia tests than the average population. Methods The 52 active older adults (22 men and 30 women, mean age: 68.4±5.6 years at the time of their first evaluation) participated in the study at two time points eight-years apart. Three sarcopenia parameters were assessed at both time points: Muscle strength (handgrip test), skeletal muscle mass index, and physical performance (gait speed), these parameters were used to diagnose sarcop0enia according to the EWGSOP2 definition. Additional motor tests were also performed at follow-up measurements to assess participants’ overall fitness. Participants self-reported physical activity and sedentary behavior using General Physical Activity Questionnaire at baseline and at follow-up measurements. Results In the first measurements we did not detect signs of sarcopenia in any individual, but after 8 years, we detected signs of sarcopenia in 7 participants. After eight years, we detected decline in ; muscle strength (-10.2%; p<.001), muscle mass index (-5.4%; p<.001), and physical performance measured with gait speed (-28.6%; p<.001). Similarly, self-reported physical activity and sedentary behavior declined, too (-25.0%; p=.030 and −48.5%; p<.001, respectively). Conclusions Despite expected lower scores on tests of sarcopenia parameters due to age-related decline, participants performed better on motor tests than reported in similar studies. Nevertheless, the prevalence of sarcopenia was consistent with most of the published literature. Trial registration The clinical trial protocol was registered on ClinicalTrials.gov, identifier: NCT04899531
Ključne besede: elderly, physical activities, sedentary behavior, skeletal muscle disorder, sarcopenia
Objavljeno v DiRROS: 29.05.2023; Ogledov: 689; Prenosov: 367
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5. Interleukin-18 is a potential biomarker linking dietary fatty acid quality and insulin resistance : results from a cross-sectional study in Northern ItalyDomenico Sergi, Juana Maria Sanz, Stefano Lazzer, Gloria Brombo, Giovanni Zuliani, Gianni Biolo, Boštjan Šimunič, Rado Pišot, Edoardo Dalla Nora, Angelina Passaro, 2023, izvirni znanstveni članek Povzetek: Dietary lipids are pivotal in modulating metabolic inflammation. Among the inflammatory mediators characterizing metabolic inflammation, interleukin 18 (IL-18) has been consistently associated with obesity and insulin resistance. This study aims to evaluate whether the quality of lipid intake impacts upon IL-18 plasma levels and the implications on insulin resistance computed by the homeostatic model assessment for insulin resistance (HOMA-IR). Using a cross-sectional design, this study confirmed that IL-18 correlated positively with insulin resistance and individuals with a HOMA-IR ≥ 2.5 displayed higher circulating IL-18 levels compared with their insulin-sensitive counterparts. In terms of the effect of the quality of dietary lipids on IL-18 circulating levels, the ratio between monounsaturated, omega-3, polyunsaturated and saturated fatty acids as well as the intake of eicosapentaenoic and docosahexaenoic acids correlated negatively with IL-18. Despite this, IL-18 circulating levels, but not dietary fatty acid quality, predicted insulin resistance. Nevertheless, the ratio between omega 3 and saturated fatty acids was a predictor of IL-18 plasma levels. Thus, the downregulation of IL-18 may underpin, at least partially, the beneficial metabolic effects of substituting omega 3 for saturated fatty acids with this cytokine potentially representing a biomarker linking dietary lipids and metabolic outcomes.
Objavljeno v DiRROS: 14.04.2023; Ogledov: 946; Prenosov: 377
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6. Irisin attenuates muscle impairment during bed rest through muscle-adipose tissue crosstalkAndrea D'Amuri, Juana Maria Sanz, Stefano Lazzer, Rado Pišot, Boštjan Šimunič, Gianni Biolo, Giovanni Zuliani, Mladen Gasparini, Marco Vicenzo Narici, Bruno Grassi, Carlo Reggiani, Edoardo Dalla Nora, Angelina Passaro, 2022, izvirni znanstveni članek Povzetek: Simple Summary: Irisin is a known myokine secreted mainly by the muscle that is produced after physical activity. It induces browning in the adipose tissue with a consequent increase in mitochondrial oxidation of lipids and reduction of insulin resistance; thus, it has been hypothesized that irisin was the molecule mediating most of the beneficial effects related to exercise on adipose tissue and consequently on the whole organism. In our study we observed that extreme physical inactivity induces the loss of muscle mass and function, and an increase in the body adipose tissue as expected. However, of note, circulating irisin levels were increased secondary to enhanced irisin synthesis mainly from adipose tissue rather than muscle. In addition, subjects who produced more irisin had reduced muscle impairment. Therefore, our hypothesis is that there is negative feedback within the muscle-adipose tissue crosstalk, specifically not only does the muscle influence the adipose tissue through irisin during exercise, but also the adipose tissue protects the muscle during inactivity.Abstract: The detrimental effect of physical inactivity on muscle characteristics are well known. Irisin, an exercise-induced myokine cleaved from membrane protein fibronectin type III domain-containing protein-5 (FNDC5), mediates at least partially the metabolic benefits of exercise. This study aimed to assess the interplay between prolonged inactivity, circulating irisin, muscle performance, muscle fibers characteristics, as well as the FNDC5 gene expression (FNDC5ge) in muscle and adipose tissue among healthy subjects. Twenty-three healthy volunteers were tested before and after 14 days of Bed Rest, (BR). Post-BR circulating levels of irisin significantly increased, whereas body composition, muscle performance, and muscle fiber characteristics deteriorated. Among the subjects achieving the highest post-BR increase of irisin, the lowest reduction in maximal voluntary contraction and specific force of Fiber Slow/1, the highest increase of FNDC5ge in adipose tissue, and no variation of FNDC5ge in skeletal muscle were recorded. Subjects who had the highest FNDC5ge in adipose tissue but not in muscle tissue showed the highest circulating irisin levels and could better withstand the harmful effect of BR.
Ključne besede: physical inactivity, bed rest, FNDC5 gene expression, myokines, sarcopenia, muscles fiber
Objavljeno v DiRROS: 07.07.2022; Ogledov: 1205; Prenosov: 652
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7. Dietary acid load but not Mediterranean diet adherence score is associated with metabolic and cardiovascular health state : ǂa ǂpopulation observational study from Northern ItalyJuana Maria Sanz, Domenico Sergi, Simona Colombari, Eleonora Capatti, Roberta Situlin, Gianni Biolo, Filippo Giorgio Di Girolamo, Stefano Lazzer, Boštjan Šimunič, Rado Pišot, Angelina Passaro, 2022, izvirni znanstveni članek Povzetek: Diet plays a pivotal role in shaping the trajectory of chronic diseases. In this regard, the Mediterranean diet has been widely shown to exert beneficial effects on cardiometabolic health. On the contrary, the Western diet, which has also been reported to be an acidogenic dietary pattern, elicits detrimental effects on both metabolic and cardiovascular (CV) health. However, the role of dietary acid load (DAL) as a predictor of cardiometabolic prognosis remains to be elucidated. Thus, this study aims to compare Mediterranean diet adherence (MDA) and DAL focusing on their relationship with metabolic and CV prognosis. A total of 448 individuals aged 55–80 years were grouped depending on their MDA, assessed using food frequency questionnaires, or DAL, evaluated using potential renal load acid (PRAL) and net-endogenous acid production (NEAP). Study participants underwent anthropometric and biochemical measurements. The metabolic syndrome (MetS) prevalence was evaluated according to the National Cholesterol Education Program-Adult Treatment Panel III. Finally, the CV risk was evaluated using three independent algorithms: atherosclerotic cardiovascular disease (ASCVD), European Systematic COronary Risk Evaluation (SCORE), and Cuore risk scores. Mediterranean diet adherence was negatively associated with PRAL and NEAP. Individuals in the higher MDA tertile group had higher HDL cholesterol as well as lower homeostasis model assessment index (HOMA-IR) and fat mass relative to the lowest MDA tertile. However, in the high-MDA tertile group, there was neither a significantly lower MetS prevalence nor CV risk. Instead, both the MetS prevalence and CV risk were higher in individuals in the higher acid PRAL quartile relative to the lower alkaline PRAL quartile. Dietary acid load, especially assessed using PRAL but not MDA, was associated with indices of metabolic and CV prognosis. Thus, DAL assessed by 24-h dietary recalls may represent a better predictor of cardiometabolic health if compared to MDA evaluated using food frequency questionnaires.
Ključne besede: Mediterranean diet, dietary acid load, alkaline diet, acidic diet, metabolic syndrome, cradiovascular risk score
Objavljeno v DiRROS: 19.05.2022; Ogledov: 1182; Prenosov: 682
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8. The aging muscle in experimental bed rest : ǂa ǂsystematic review and meta-analysisFilippo Giorgio Di Girolamo, Nicola Fiotti, Zoran Milanović, Roberta Situlin, Filippo Mearelli, Pierandrea Vinci, Boštjan Šimunič, Rado Pišot, Marco Vicenzo Narici, Gianni Biolo, 2021, pregledni znanstveni članek Povzetek: Background: Maintaining skeletal muscle mass and function in aging is crucial for preserving the quality of life and health. An experimental bed rest (BR) protocol is a suitable model to explore muscle decline on aging during inactivity. Objective: The purpose of this systematic review and meta-analysis was, therefore, to carry out an up-to-date evaluation of bed rest, with a specific focus on the magnitude of effects on muscle mass, strength, power, and functional capacity changes as well as the mechanisms, molecules, and pathways involved in muscle decay. Design: This was a systematic review and meta-analysis study. Data sources: We used PubMed, Medline; Web of Science, Google Scholar, and the Cochrane library, all of which were searched prior to April 23, 2020. A manual search was performed to cover bed rest experimental protocols using the following key terms, either singly or in combination: %Elderly Bed rest,% %Older Bed rest,% %Old Bed rest,% %Aging Bed rest,% %Aging Bed rest,% %Bed-rest,% and %Bedrest%. Eligibility criteria for selecting studies: The inclusion criteria were divided into four sections: type of study, participants, interventions, and outcome measures. The primary outcome measures were: body mass index, fat mass, fat-free mass, leg lean mass, cross-sectional area, knee extension power, cytokine pattern, IGF signaling biomarkers, FOXO signaling biomarkers, mitochondrial modulation biomarkers, and muscle protein kinetics biomarkers. Results: A total of 25 studies were included in the qualitative synthesis, while 17 of them were included in the meta-analysis. In total, 118 healthy elderly volunteers underwent 5-, 7-, 10-, or 14-days of BR and provided a brief sketch on the possible mechanisms involved. In the very early phase of BR, important changes occurred in the skeletal muscle, with significant loss of performance associated with a lesser grade reduction of the total body and muscle mass. Meta-analysis of the effect of bed rest on total body mass was determined to be small but statistically significant (ES = %0.45, 95% CI: %0.72 to %0.19, P < 0.001). Moderate, statistically significant effects were observed for total lean body mass (ES = %0.67, 95% CI: %0.95 to %0.40, P < 0.001) after bed rest intervention. Overall, total lean body mass was decreased by 1.5 kg, while there was no relationship between bed rest duration and outcomes (Z = 0.423, p = 672). The meta-analyzed effect showed that bed rest produced large, statistically significant, effects (ES = %1.06, 95% CI: %1.37 to %0.75, P < 0.001) in terms of the knee extension power. Knee extension power was decreased by 14.65 N/s. In contrast, to other measures, meta-regression showed a significant relationship between bed rest duration and knee extension power (Z = 4.219, p < 0.001). Moderate, statistically significant, effects were observed after bed rest intervention for leg muscle mass in both old (ES = %0.68, 95% CI: %0.96 to %0.40, P < 0.001) and young (ES = %0.51, 95% CI: %0.80 to %0.22, P < 0.001) adults. However, the magnitude of change was higher in older (MD = %0.86 kg) compared to younger (MD = %0.24 kg) adults. Conclusion: Experimental BR is a suitable model to explore the detrimental effects of inactivity in young adults, old adults, and hospitalized people. Changes in muscle mass and function are the two most investigated variables, and they allow for a consistent trend in the BR-induced changes. Mechanisms underlying the greater loss of muscle mass and function in aging, following inactivity, need to be thoroughly investigated.
Ključne besede: bed rest, aging, muscles, muscle physiopathology, muscle function
Objavljeno v DiRROS: 26.08.2021; Ogledov: 2039; Prenosov: 1273
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9. Impact of sedentarism due to the COVID-19 home confinement on neuromuscular, cardiovascular and metabolic health : physiological and pathophysiological implications and recommendations for physical and nutritional countermeasuresMarco Vicenzo Narici, Giuseppe De Vito, Martino V. Franchi, Antonio Paoli, Tatiana Moro, Giuseppe Marcolin, Bruno Grassi, Giovanni Baldassarre, Lucrezia Zuccarelli, Gianni Biolo, Filippo Giorgio Di Girolamo, Nicola Fiotti, F. Dela, Paul L. Greenhaff, Constantinos Maganaris, 2020, izvirni znanstveni članek Ključne besede: COVID-19, sedentarism, neuromuscular system, cardiovascular system, glucose homeostasis, body composition, nutrition, exercise
Objavljeno v DiRROS: 18.12.2020; Ogledov: 1817; Prenosov: 427
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