TY - JOUR A1 - Chaabene, Helmi A1 - Behm, David George A1 - Negra, Yassine A1 - Granacher, Urs T1 - Acute Effects of Static Stretching on Muscle Strength and Power BT - An Attempt to Clarify Previous Caveats JF - Frontiers in Physiology N2 - The effects of static stretching (StS) on subsequent strength and power activities has been one of the most debated topics in sport science literature over the past decades. The aim of this review is (1) to summarize previous and current findings on the acute effects of StS on muscle strength and power performances; (2) to update readers’ knowledge related to previous caveats; and (3) to discuss the underlying physiological mechanisms of short-duration StS when performed as single-mode treatment or when integrated into a full warm-up routine. Over the last two decades, StS has been considered harmful to subsequent strength and power performances. Accordingly, it has been recommended not to apply StS before strength- and power-related activities. More recent evidence suggests that when performed as a single-mode treatment or when integrated within a full warm-up routine including aerobic activity, dynamic-stretching, and sport-specific activities, short-duration StS (≤60 s per muscle group) trivially impairs subsequent strength and power activities (∆1–2%). Yet, longer StS durations (>60 s per muscle group) appear to induce substantial and practically relevant declines in strength and power performances (∆4.0–7.5%). Moreover, recent evidence suggests that when included in a full warm-up routine, short-duration StS may even contribute to lower the risk of sustaining musculotendinous injuries especially with high-intensity activities (e.g., sprint running and change of direction speed). It seems that during short-duration StS, neuromuscular activation and musculotendinous stiffness appear not to be affected compared with long-duration StS. Among other factors, this could be due to an elevated muscle temperature induced by a dynamic warm-up program. More specifically, elevated muscle temperature leads to increased muscle fiber conduction-velocity and improved binding of contractile proteins (actin, myosin). Therefore, our previous understanding of harmful StS effects on subsequent strength and power activities has to be updated. In fact, short-duration StS should be included as an important warm-up component before the uptake of recreational sports activities due to its potential positive effect on flexibility and musculotendinous injury prevention. However, in high-performance athletes, short-duration StS has to be applied with caution due to its negligible but still prevalent negative effects on subsequent strength and power performances, which could have an impact on performance during competition. KW - passive stretching KW - physical fitness KW - physiology KW - range of motion KW - injury Y1 - 2019 U6 - https://doi.org/10.3389/fphys.2019.01468 SN - 1664-042X VL - 10 PB - Frontiers Research Foundation CY - Lausanne ER - TY - GEN A1 - Chaabene, Helmi A1 - Behm, David George A1 - Negra, Yassine A1 - Granacher, Urs T1 - Acute Effects of Static Stretching on Muscle Strength and Power BT - An Attempt to Clarify Previous Caveats T2 - Postprints der Universität Potsdam Humanwissenschaftliche Reihe N2 - The effects of static stretching (StS) on subsequent strength and power activities has been one of the most debated topics in sport science literature over the past decades. The aim of this review is (1) to summarize previous and current findings on the acute effects of StS on muscle strength and power performances; (2) to update readers’ knowledge related to previous caveats; and (3) to discuss the underlying physiological mechanisms of short-duration StS when performed as single-mode treatment or when integrated into a full warm-up routine. Over the last two decades, StS has been considered harmful to subsequent strength and power performances. Accordingly, it has been recommended not to apply StS before strength- and power-related activities. More recent evidence suggests that when performed as a single-mode treatment or when integrated within a full warm-up routine including aerobic activity, dynamic-stretching, and sport-specific activities, short-duration StS (≤60 s per muscle group) trivially impairs subsequent strength and power activities (∆1–2%). Yet, longer StS durations (>60 s per muscle group) appear to induce substantial and practically relevant declines in strength and power performances (∆4.0–7.5%). Moreover, recent evidence suggests that when included in a full warm-up routine, short-duration StS may even contribute to lower the risk of sustaining musculotendinous injuries especially with high-intensity activities (e.g., sprint running and change of direction speed). It seems that during short-duration StS, neuromuscular activation and musculotendinous stiffness appear not to be affected compared with long-duration StS. Among other factors, this could be due to an elevated muscle temperature induced by a dynamic warm-up program. More specifically, elevated muscle temperature leads to increased muscle fiber conduction-velocity and improved binding of contractile proteins (actin, myosin). Therefore, our previous understanding of harmful StS effects on subsequent strength and power activities has to be updated. In fact, short-duration StS should be included as an important warm-up component before the uptake of recreational sports activities due to its potential positive effect on flexibility and musculotendinous injury prevention. However, in high-performance athletes, short-duration StS has to be applied with caution due to its negligible but still prevalent negative effects on subsequent strength and power performances, which could have an impact on performance during competition. T3 - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe - 585 KW - passive stretching KW - physical fitness KW - physiology KW - range of motion KW - injury Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-440036 SN - 1866-8364 IS - 585 ER - TY - GEN A1 - Saidi, Karim A1 - Zouhal, Hassane A1 - Rhibi, Fatma A1 - Tijani, Jed M. A1 - Boullosa, Daniel A1 - Chebbi, Amel A1 - Hackney, Anthony C. A1 - Granacher, Urs A1 - Bideau, Benoit A1 - Ben Abderrahman, Abderraouf T1 - Effects of a six-week period of congested match play on plasma volume variations, hematological parameters, training workload and physical fitness in elite soccer players T2 - Postprints der Universität Potsdam Humanwissenschaftliche Reihe N2 - Objectives The aims of this study were to investigate the effects of a six-week in-season period of soccer training and games (congested period) on plasma volume variations (PV), hematological parameters, and physical fitness in elite players. In addition, we analyzed relationships between training load, hematological parameters and players’ physical fitness. Methods Eighteen elite players were evaluated before (T1) and after (T2) a six-week in-season period interspersed with 10 soccer matches. At T1 and T2, players performed the Yo-Yo intermittent recovery test level 1 (YYIR1), the repeated shuttle sprint ability test (RSSA), the countermovement jump test (CMJ), and the squat jump test (SJ). In addition, PV and hematological parameters (erythrocytes [M/mm3], hematocrit [%], hemoglobin [g/dl], mean corpuscular volume [fl], mean corpuscular hemoglobin content [pg], and mean hemoglobin concentration [%]) were assessed. Daily ratings of perceived exertion (RPE) were monitored in order to quantify the internal training load. Results From T1 to T2, significant performance declines were found for the YYIR1 (p<0.001, effect size [ES] = 0.5), RSSA (p<0.01, ES = 0.6) and SJ tests (p< 0.046, ES = 0.7). However, no significant changes were found for the CMJ (p = 0.86, ES = 0.1). Post-exercise, RSSA blood lactate (p<0.012, ES = 0.2) and PV (p<0.01, ES = 0.7) increased significantly from T1 to T2. A significant decrease was found from T1 to T2 for the erythrocyte value (p<0.002, ES = 0.5) and the hemoglobin concentration (p<0.018, ES = 0.8). The hematocrit percentage rate was also significantly lower (p<0.001, ES = 0.6) at T2. The mean corpuscular volume, mean corpuscular hemoglobin content and the mean hemoglobin content values were not statistically different from T1 to T2. No significant relationships were detected between training load parameters and percentage changes of hematological parameters. However, a significant relationship was observed between training load and changes in RSSA performance (r = -0.60; p<0.003). Conclusions An intensive period of “congested match play” over 6 weeks significantly compromised players’ physical fitness. These changes were not related to hematological parameters, even though significant alterations were detected for selected measures. T3 - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe - 572 KW - body density KW - performance KW - exercise KW - blood KW - hematocrit KW - responses KW - physiology KW - schedule KW - recovery KW - fatigue Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-437166 SN - 1866-8364 IS - 572 ER - TY - JOUR A1 - Saidi, Karim A1 - Zouhal, Hassane A1 - Rhibi, Fatma A1 - Tijani, Jed M. A1 - Boullosa, Daniel A1 - Chebbi, Amel A1 - Hackney, Anthony C. A1 - Granacher, Urs A1 - Bideau, Benoit A1 - Ben Abderrahman, Abderraouf T1 - Effects of a six-week period of congested match play on plasma volume variations, hematological parameters, training workload and physical fitness in elite soccer players JF - PLOS ONE N2 - Objectives The aims of this study were to investigate the effects of a six-week in-season period of soccer training and games (congested period) on plasma volume variations (PV), hematological parameters, and physical fitness in elite players. In addition, we analyzed relationships between training load, hematological parameters and players’ physical fitness. Methods Eighteen elite players were evaluated before (T1) and after (T2) a six-week in-season period interspersed with 10 soccer matches. At T1 and T2, players performed the Yo-Yo intermittent recovery test level 1 (YYIR1), the repeated shuttle sprint ability test (RSSA), the countermovement jump test (CMJ), and the squat jump test (SJ). In addition, PV and hematological parameters (erythrocytes [M/mm3], hematocrit [%], hemoglobin [g/dl], mean corpuscular volume [fl], mean corpuscular hemoglobin content [pg], and mean hemoglobin concentration [%]) were assessed. Daily ratings of perceived exertion (RPE) were monitored in order to quantify the internal training load. Results From T1 to T2, significant performance declines were found for the YYIR1 (p<0.001, effect size [ES] = 0.5), RSSA (p<0.01, ES = 0.6) and SJ tests (p< 0.046, ES = 0.7). However, no significant changes were found for the CMJ (p = 0.86, ES = 0.1). Post-exercise, RSSA blood lactate (p<0.012, ES = 0.2) and PV (p<0.01, ES = 0.7) increased significantly from T1 to T2. A significant decrease was found from T1 to T2 for the erythrocyte value (p<0.002, ES = 0.5) and the hemoglobin concentration (p<0.018, ES = 0.8). The hematocrit percentage rate was also significantly lower (p<0.001, ES = 0.6) at T2. The mean corpuscular volume, mean corpuscular hemoglobin content and the mean hemoglobin content values were not statistically different from T1 to T2. No significant relationships were detected between training load parameters and percentage changes of hematological parameters. However, a significant relationship was observed between training load and changes in RSSA performance (r = -0.60; p<0.003). Conclusions An intensive period of “congested match play” over 6 weeks significantly compromised players’ physical fitness. These changes were not related to hematological parameters, even though significant alterations were detected for selected measures. KW - body density KW - performance KW - exercise KW - blood KW - hematocrit KW - responses KW - physiology KW - schedule KW - recovery KW - fatigue Y1 - 2019 U6 - https://doi.org/10.1371/journal.pone.0219692 SN - 1932-6203 VL - 14 IS - 7 PB - Public Library of Science CY - San Francisco ER - TY - JOUR A1 - Lesinski, Melanie A1 - Schmelcher, Alina A1 - Herz, Michael A1 - Puta, Christian A1 - Gabriel, Holger A1 - Arampatzis, Adamantios A1 - Laube, Gunnar A1 - Büsch, Dirk A1 - Granacher, Urs T1 - Maturation-, age-, and sex-specific anthropometric and physical fitness percentiles of German elite young athletes JF - Plos One N2 - The aim of this study was to establish maturation-, age-, and sex-specific anthropometric and physical fitness percentile reference values of young elite athletes from various sports. Anthropometric (i.e., standing and sitting body height, body mass, body mass index) and physical fitness (i.e., countermovement jump, drop jump, change-of-direction speed [i.e., T-test], trunk muscle endurance [i.e., ventral Bourban test], dynamic lower limbs balance [i.e., Y-balance test], hand grip strength) of 703 male and female elite young athletes aged 8–18 years were collected to aggregate reference values according to maturation, age, and sex. Findings indicate that body height and mass were significantly higher (p<0.001; 0.95≤d≤1.74) in more compared to less mature young athletes as well as with increasing chronological age (p<0.05; 0.66≤d≤3.13). Furthermore, male young athletes were significantly taller and heavier compared to their female counterparts (p<0.001; 0.34≤d≤0.50). In terms of physical fitness, post-pubertal athletes showed better countermovement jump, drop jump, change-of-direction, and handgrip strength performances (p<0.001; 1.57≤d≤8.72) compared to pubertal athletes. Further, countermovement jump, drop jump, change-of-direction, and handgrip strength performances increased with increasing chronological age (p<0.05; 0.29≤d≤4.13). In addition, male athletes outperformed their female counterpart in the countermovement jump, drop jump, change-of-direction, and handgrip strength (p<0.05; 0.17≤d≤0.76). Significant age by sex interactions indicate that sex-specific differences were even more pronounced with increasing age. Conclusively, body height, body mass, and physical fitness increased with increasing maturational status and chronological age. Sex-specific differences appear to be larger as youth grow older. Practitioners can use the percentile values as approximate benchmarks for talent identification and development. KW - biological maturation KW - reliability KW - validity KW - performance KW - physiology KW - maturity KW - injury KW - talent Y1 - 2020 U6 - https://doi.org/10.1371/journal.pone.0237423 SN - 1932-6203 VL - 15 IS - 8 PB - Plos One CY - San Francisco, California ER - TY - GEN A1 - Lesinski, Melanie A1 - Schmelcher, Alina A1 - Herz, Michael A1 - Puta, Christian A1 - Gabriel, Holger A1 - Arampatzis, Adamantios A1 - Laube, Gunnar A1 - Büsch, Dirk A1 - Granacher, Urs T1 - Maturation-, age-, and sex-specific anthropometric and physical fitness percentiles of German elite young athletes T2 - Postprints der Universität Potsdam : Humanwissenschaftliche Reihe N2 - The aim of this study was to establish maturation-, age-, and sex-specific anthropometric and physical fitness percentile reference values of young elite athletes from various sports. Anthropometric (i.e., standing and sitting body height, body mass, body mass index) and physical fitness (i.e., countermovement jump, drop jump, change-of-direction speed [i.e., T-test], trunk muscle endurance [i.e., ventral Bourban test], dynamic lower limbs balance [i.e., Y-balance test], hand grip strength) of 703 male and female elite young athletes aged 8–18 years were collected to aggregate reference values according to maturation, age, and sex. Findings indicate that body height and mass were significantly higher (p<0.001; 0.95≤d≤1.74) in more compared to less mature young athletes as well as with increasing chronological age (p<0.05; 0.66≤d≤3.13). Furthermore, male young athletes were significantly taller and heavier compared to their female counterparts (p<0.001; 0.34≤d≤0.50). In terms of physical fitness, post-pubertal athletes showed better countermovement jump, drop jump, change-of-direction, and handgrip strength performances (p<0.001; 1.57≤d≤8.72) compared to pubertal athletes. Further, countermovement jump, drop jump, change-of-direction, and handgrip strength performances increased with increasing chronological age (p<0.05; 0.29≤d≤4.13). In addition, male athletes outperformed their female counterpart in the countermovement jump, drop jump, change-of-direction, and handgrip strength (p<0.05; 0.17≤d≤0.76). Significant age by sex interactions indicate that sex-specific differences were even more pronounced with increasing age. Conclusively, body height, body mass, and physical fitness increased with increasing maturational status and chronological age. Sex-specific differences appear to be larger as youth grow older. Practitioners can use the percentile values as approximate benchmarks for talent identification and development. T3 - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe - 662 KW - biological maturation KW - reliability KW - validity KW - performance KW - physiology KW - maturity KW - injury KW - talent Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-480268 SN - 1866-8364 IS - 662 ER - TY - GEN A1 - Clegg, Mark R. A1 - Wacker, Alexander A1 - Spijkerman, Elly T1 - Phenotypic Diversity and Plasticity of Photoresponse Across an Environmentally Contrasting Family of Phytoflagellates T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Organisms often employ ecophysiological strategies to exploit environmental conditions and ensure bio-energetic success. However, the many complexities involved in the differential expression and flexibility of these strategies are rarely fully understood. Therefore, for the first time, using a three-part cross-disciplinary laboratory experimental analysis, we investigated the diversity and plasticity of photoresponsive traits employed by one family of environmentally contrasting, ecologically important phytoflagellates. The results demonstrated an extensive inter-species phenotypic diversity of behavioural, physiological, and compositional photoresponse across the Chlamydomonadaceae, and a multifaceted intra-species phenotypic plasticity, involving a broad range of beneficial photoacclimation strategies, often attributable to environmental predisposition and phylogenetic differentiation. Deceptively diverse and sophisticated strong (population and individual cell) behavioural photoresponses were observed, with divergence from a general preference for low light (and flexibility) dictated by intra-familial differences in typical habitat (salinity and trophy) and phylogeny. Notably, contrasting lower, narrow, and flexible compared with higher, broad, and stable preferences were observed in freshwater vs. brackish and marine species. Complex diversity and plasticity in physiological and compositional photoresponses were also discovered. Metabolic characteristics (such as growth rates, respiratory costs and photosynthetic capacity, efficiency, compensation and saturation points) varied elaborately with species, typical habitat (often varying more in eutrophic species, such as Chlamydomonas reinhardtii), and culture irradiance (adjusting to optimise energy acquisition and suggesting some propensity for low light). Considerable variations in intracellular pigment and biochemical composition were also recorded. Photosynthetic and accessory pigments (such as chlorophyll a, xanthophyll-cycle components, chlorophyll a:b and chlorophyll a:carotenoid ratios, fatty acid content and saturation ratios) varied with phylogeny and typical habitat (to attune photosystem ratios in different trophic conditions and to optimise shade adaptation, photoprotection, and thylakoid architecture, particularly in freshwater environments), and changed with irradiance (as reaction and harvesting centres adjusted to modulate absorption and quantum yield). The complex, concomitant nature of the results also advocated an integrative approach in future investigations. Overall, these nuanced, diverse, and flexible photoresponsive traits will greatly contribute to the functional ecology of these organisms, addressing environmental heterogeneity and potentially shaping individual fitness, spatial and temporal distribution, prevalence, and ecosystem dynamics. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1219 KW - photoresponse KW - behaviour KW - physiology KW - composition KW - photosynthesis KW - acclimation KW - Chlamydomonas KW - ecophysiology Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-536174 SN - 1866-8372 IS - 1219 ER - TY - JOUR A1 - Clegg, Mark R. A1 - Wacker, Alexander A1 - Spijkerman, Elly T1 - Phenotypic Diversity and Plasticity of Photoresponse Across an Environmentally Contrasting Family of Phytoflagellates JF - Frontiers in plant science : FPLS N2 - Organisms often employ ecophysiological strategies to exploit environmental conditions and ensure bio-energetic success. However, the many complexities involved in the differential expression and flexibility of these strategies are rarely fully understood. Therefore, for the first time, using a three-part cross-disciplinary laboratory experimental analysis, we investigated the diversity and plasticity of photoresponsive traits employed by one family of environmentally contrasting, ecologically important phytoflagellates. The results demonstrated an extensive inter-species phenotypic diversity of behavioural, physiological, and compositional photoresponse across the Chlamydomonadaceae, and a multifaceted intra-species phenotypic plasticity, involving a broad range of beneficial photoacclimation strategies, often attributable to environmental predisposition and phylogenetic differentiation. Deceptively diverse and sophisticated strong (population and individual cell) behavioural photoresponses were observed, with divergence from a general preference for low light (and flexibility) dictated by intra-familial differences in typical habitat (salinity and trophy) and phylogeny. Notably, contrasting lower, narrow, and flexible compared with higher, broad, and stable preferences were observed in freshwater vs. brackish and marine species. Complex diversity and plasticity in physiological and compositional photoresponses were also discovered. Metabolic characteristics (such as growth rates, respiratory costs and photosynthetic capacity, efficiency, compensation and saturation points) varied elaborately with species, typical habitat (often varying more in eutrophic species, such as Chlamydomonas reinhardtii), and culture irradiance (adjusting to optimise energy acquisition and suggesting some propensity for low light). Considerable variations in intracellular pigment and biochemical composition were also recorded. Photosynthetic and accessory pigments (such as chlorophyll a, xanthophyll-cycle components, chlorophyll a:b and chlorophyll a:carotenoid ratios, fatty acid content and saturation ratios) varied with phylogeny and typical habitat (to attune photosystem ratios in different trophic conditions and to optimise shade adaptation, photoprotection, and thylakoid architecture, particularly in freshwater environments), and changed with irradiance (as reaction and harvesting centres adjusted to modulate absorption and quantum yield). The complex, concomitant nature of the results also advocated an integrative approach in future investigations. Overall, these nuanced, diverse, and flexible photoresponsive traits will greatly contribute to the functional ecology of these organisms, addressing environmental heterogeneity and potentially shaping individual fitness, spatial and temporal distribution, prevalence, and ecosystem dynamics. KW - photoresponse KW - behaviour KW - physiology KW - composition KW - photosynthesis KW - acclimation KW - Chlamydomonas KW - ecophysiology Y1 - 2021 U6 - https://doi.org/10.3389/fpls.2021.707541 SN - 1664-462X IS - 12 PB - Frontiers Media CY - Lausanne ER - TY - THES A1 - Igual Gil, Carla T1 - Role of the GDF15-GFRAL pathway under skeletal muscle mitochondrial stress T1 - Funktion des GDF15-GFRAL Signaltransduktionsweges bei mitochondrialem Stress im Skelettmuskel N2 - Growth differentiation factor 15 (GDF15) is a stress-induced cytokine secreted into the circulation by a number of tissues under different pathological conditions such as cardiovascular disease, cancer or mitochondrial dysfunction, among others. While GDF15 signaling through its recently identified hindbrain-specific receptor GDNF family receptor alpha-like (GFRAL) has been proposed to be involved in the metabolic stress response, its endocrine role under chronic stress conditions is still poorly understood. Mitochondrial dysfunction is characterized by the impairment of oxidative phosphorylation (OXPHOS), leading to inefficient functioning of mitochondria and consequently, to mitochondrial stress. Importantly, mitochondrial dysfunction is among the pathologies to most robustly induce GDF15 as a cytokine in the circulation. The overall aim of this thesis was to elucidate the role of the GDF15-GFRAL pathway under mitochondrial stress conditions. For this purpose, a mouse model of skeletal muscle-specific mitochondrial stress achieved by ectopic expression of uncoupling protein 1 (UCP1), the HSA-Ucp1-transgenic (TG) mouse, was employed. As a consequence of mitochondrial stress, TG mice display a metabolic remodeling consisting of a lean phenotype, an improved glucose metabolism, an increased metabolic flexibility and a metabolic activation of white adipose tissue. Making use of TG mice crossed with whole body Gdf15-knockout (GdKO) and Gfral-knockout (GfKO) mouse models, this thesis demonstrates that skeletal muscle mitochondrial stress induces the integrated stress response (ISR) and GDF15 in skeletal muscle, which is released into the circulation as a myokine (muscle-induced cytokine) in a circadian manner. Further, this work identifies GDF15-GFRAL signaling to be responsible for the systemic metabolic remodeling elicited by mitochondrial stress in TG mice. Moreover, this study reveals a daytime-restricted anorexia induced by the GDF15-GFRAL axis under muscle mitochondrial stress, which is, mechanistically, mediated through the induction of hypothalamic corticotropin releasing hormone (CRH). Finally, this work elucidates a so far unknown physiological outcome of the GDF15-GFRAL pathway: the induction of anxiety-like behavior. In conclusion, this study uncovers a muscle-brain crosstalk under skeletal muscle mitochondrial stress conditions through the induction of GDF15 as a myokine that signals through the hindbrain-specific GFRAL receptor to elicit a stress response leading to metabolic remodeling and modulation of ingestive- and anxiety-like behavior. N2 - Der Wachstum- und Differenzierungsfaktor 15 (GDF15) ist ein stressinduziertes Zytokin, dass bei u.a. Krebs, kardiovaskulären oder mitochondrialer Erkrankungen in den betroffenen Geweben stark induziert und ins Blut sekretiert werden kann. Die endokrine Funktion von GDF15 sowie die Bedeutung des kürzlich identifizierten und spezifisch im Hirnstamm exprimierten GDF15-Rezeptors GFRAL (GDNF family receptor alpha-like) unter chronischen Stressbedingungen ist jedoch noch unzureichend verstanden. Mitochondrialer Stress ist durch eine Fehlfunktion der oxidativen Phosphorylierung (OXPHOS) charakterisiert, was eine ineffiziente ATP-Synthese und eine gestörte zelluläre Energiehomöostase zur Folge hat. Ziel der Doktorarbeit war es, die biologische Funktion des GDF15-GFRAL-Signalwegs unter mitochondrialen Stressbedingungen aufzuklären. Zu diesem Zweck wurde das etablierte transgene HSA-Ucp1-Mausmodel (TG) untersucht, welches durch eine chronisch verringerte OXPHOS-Effizienz spezifisch im Skelettmuskel sowie eine systemische Anpassung des Energiestoffwechsels charakterisiert ist. Dabei konnte in dieser Arbeit zunächst zeigt werden, dass mitochondrialer Stress im Skelettmuskel zell-autonom eine integrierte Stressantwort (ISR) induziert, wodurch die Expression und Sekretion von GDF15 in den Blutkreislauf als Myokin (muskelinduziertes Zytokin) stark erhöht wird. Zudem konnte erstmalig eine tageszeitliche Schwankung der muskulären Gdf15 Genexpression und der im Blut zirkulierenden GDF15-Level bei TG Mäusen identifiziert werden. Durch weiterführende Zuchtkreuzungen der TG-Mäuse mit konstitutiven Knockout-Mäusen (KO) zur Inaktivierung der Gene Gdf15 (GdKO) oder Gfral (GfKO), konnte zudem gezeigt werden, dass sowohl durch das zirkulierende GDF15 als auch die Aktivierung der GFRAL-Signalachse eine Tageszeit-abhängige Anorexie sowie die systemische Anpassung des Energiestoffwechsels im TG Mausmodell vermittelt werden. Mechanistisch konnte dabei erstmalig eine GFRAL-abhängige Induktion von Corticotropin-releasing Hormone (CRH) im Hypothalamus sowie ein erhöhtes, GFRAL-abhängiges Angstverhalten in TG Mäuse beschrieben werden. Zusammenfassend unterstreichen die Ergebnisse die systemische Rolle von GDF15 als Myokin und die Bedeutung der endokrinen Kommunikation zwischen Skelettmuskel und Gehirn, vermittelt durch GDF15-GFRAL Signalachse, für die Energiehomöostase bei mitochondrialer Fehlfunktion. Die gewonnen Erkenntnisse dieser Doktorarbeit können somit zur Entwicklung neuer Therapieansätze für Patienten mit einer mitochondrialen bzw. Stoffwechselerkrankung beitragen. KW - GDF15 KW - mitochondria KW - physiology KW - metabolism KW - GDF15 KW - Stoffwechsel KW - Mitochondrien KW - Physiologie Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-554693 ER -