TY - JOUR A1 - Wei, Xiaoyan A1 - Franke, Julia A1 - Ost, Mario A1 - Wardelmann, Kristina A1 - Börno, Stefan A1 - Timmermann, Bernd A1 - Meierhofer, David A1 - Kleinridders, Andre A1 - Klaus, Susanne A1 - Stricker, Sigmar T1 - Cell autonomous requirement of neurofibromin (Nf1) for postnatal muscle hypertrophic growth and metabolic homeostasis JF - Journal of cachexia, sarcopenia and muscle N2 - Background Neurofibromatosis type 1 (NF1) is a multi-organ disease caused by mutations in neurofibromin 1 (NF1). Amongst other features, NF1 patients frequently show reduced muscle mass and strength, impairing patients' mobility and increasing the risk of fall. The role of Nf1 in muscle and the cause for the NF1-associated myopathy are mostly unknown. Methods To dissect the function ofNf1in muscle, we created muscle-specific knockout mouse models for NF1, inactivatingNf1in the prenatal myogenic lineage either under the Lbx1 promoter or under the Myf5 promoter. Mice were analysed during prenatal and postnatal myogenesis and muscle growth. Results Nf1(Lbx1)and Nf1(Myf5)animals showed only mild defects in prenatal myogenesis. Nf1(Lbx1)animals were perinatally lethal, while Nf1(Myf5)animals survived only up to approximately 25 weeks. A comprehensive phenotypic characterization of Nf1(Myf5)animals showed decreased postnatal growth, reduced muscle size, and fast fibre atrophy. Proteome and transcriptome analyses of muscle tissue indicated decreased protein synthesis and increased proteasomal degradation, and decreased glycolytic and increased oxidative activity in muscle tissue. High-resolution respirometry confirmed enhanced oxidative metabolism in Nf1(Myf5)muscles, which was concomitant to a fibre type shift from type 2B to type 2A and type 1. Moreover, Nf1(Myf5)muscles showed hallmarks of decreased activation of mTORC1 and increased expression of atrogenes. Remarkably, loss of Nf1 promoted a robust activation of AMPK with a gene expression profile indicative of increased fatty acid catabolism. Additionally, we observed a strong induction of genes encoding catabolic cytokines in muscle Nf1(Myf5)animals, in line with a drastic reduction of white, but not brown adipose tissue. Conclusions Our results demonstrate a cell autonomous role for Nf1 in myogenic cells during postnatal muscle growth required for metabolic and proteostatic homeostasis. Furthermore, Nf1 deficiency in muscle drives cross-tissue communication and mobilization of lipid reserves. KW - neurofibromatosis KW - NF1 KW - myopathy KW - muscle atrophy KW - muscle metabolism KW - muscle fibre type KW - AMPK Y1 - 2020 U6 - https://doi.org/10.1002/jcsm.12632 SN - 2190-5991 SN - 2190-6009 VL - 11 IS - 6 SP - 1758 EP - 1778 PB - Wiley CY - Hoboken ER - TY - GEN A1 - Delfan, Maryam A1 - Vahed, Alieh A1 - Bishop, David A1 - Juybari, Raheleh Amadeh A1 - Laher, Ismail A1 - Saeidi, Ayoub A1 - Granacher, Urs A1 - Zouhal, Hassane T1 - Effects of two workload-matched high intensity interval training protocols on regulatory factors associated with mitochondrial biogenesis in the soleus muscle of diabetic rats T2 - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe N2 - Aims: High intensity interval training (HIIT) improves mitochondrial characteristics. This study compared the impact of two workload-matched high intensity interval training (HIIT) protocols with different work:recovery ratios on regulatory factors related to mitochondrial biogenesis in the soleus muscle of diabetic rats. Materials and methods: Twenty-four Wistar rats were randomly divided into four equal-sized groups: non-diabetic control, diabetic control (DC), diabetic with long recovery exercise [4–5 × 2-min running at 80%–90% of the maximum speed reached with 2-min of recovery at 40% of the maximum speed reached (DHIIT1:1)], and diabetic with short recovery exercise (5–6 × 2-min running at 80%–90% of the maximum speed reached with 1-min of recovery at 30% of the maximum speed reached [DHIIT2:1]). Both HIIT protocols were completed five times/week for 4 weeks while maintaining equal running distances in each session. Results: Gene and protein expressions of PGC-1α, p53, and citrate synthase of the muscles increased significantly following DHIIT1:1 and DHIIT2:1 compared to DC (p ˂ 0.05). Most parameters, except for PGC-1α protein (p = 0.597), were significantly higher in DHIIT2:1 than in DHIIT1:1 (p ˂ 0.05). Both DHIIT groups showed significant increases in maximum speed with larger increases in DHIIT2:1 compared with DHIIT1:1. Conclusion: Our findings indicate that both HIIT protocols can potently up-regulate gene and protein expression of PGC-1α, p53, and CS. However, DHIIT2:1 has superior effects compared with DHIIT1:1 in improving mitochondrial adaptive responses in diabetic rats. T3 - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe - 794 KW - diabetes mellitus KW - muscle metabolism KW - time-efficient exercise KW - mitochondrial adaptation KW - exercise training Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-564441 SN - 1866-8364 SP - 1 EP - 12 PB - Universitätsverlag Potsdam CY - Potsdam ER - TY - JOUR A1 - Delfan, Maryam A1 - Vahed, Alieh A1 - Bishop, David A1 - Juybari, Raheleh Amadeh A1 - Laher, Ismail A1 - Saeidi, Ayoub A1 - Granacher, Urs A1 - Zouhal, Hassane T1 - Effects of two workload-matched high-intensity interval training protocols on regulatory factors associated with mitochondrial biogenesis in the soleus muscle of diabetic rats JF - Frontiers in Physiology N2 - Aims: High intensity interval training (HIIT) improves mitochondrial characteristics. This study compared the impact of two workload-matched high intensity interval training (HIIT) protocols with different work:recovery ratios on regulatory factors related to mitochondrial biogenesis in the soleus muscle of diabetic rats. Materials and methods: Twenty-four Wistar rats were randomly divided into four equal-sized groups: non-diabetic control, diabetic control (DC), diabetic with long recovery exercise [4–5 × 2-min running at 80%–90% of the maximum speed reached with 2-min of recovery at 40% of the maximum speed reached (DHIIT1:1)], and diabetic with short recovery exercise (5–6 × 2-min running at 80%–90% of the maximum speed reached with 1-min of recovery at 30% of the maximum speed reached [DHIIT2:1]). Both HIIT protocols were completed five times/week for 4 weeks while maintaining equal running distances in each session. Results: Gene and protein expressions of PGC-1α, p53, and citrate synthase of the muscles increased significantly following DHIIT1:1 and DHIIT2:1 compared to DC (p ˂ 0.05). Most parameters, except for PGC-1α protein (p = 0.597), were significantly higher in DHIIT2:1 than in DHIIT1:1 (p ˂ 0.05). Both DHIIT groups showed significant increases in maximum speed with larger increases in DHIIT2:1 compared with DHIIT1:1. Conclusion: Our findings indicate that both HIIT protocols can potently up-regulate gene and protein expression of PGC-1α, p53, and CS. However, DHIIT2:1 has superior effects compared with DHIIT1:1 in improving mitochondrial adaptive responses in diabetic rats. KW - diabetes mellitus KW - muscle metabolism KW - time-efficient exercise KW - mitochondrial adaptation KW - exercise training Y1 - 2022 U6 - https://doi.org/10.3389/fphys.2022.927969 SN - 1664-042X SP - 1 EP - 12 PB - Frontiers CY - Lausanne, Schweiz ER -