Project description:The objective of this study was to identify novel genes whose expression is sensitive to anabolic stimuli. We used microarrays to detail the change in gene expression within the tibialis anterior muscle following an anabolic stimulus. In this case, the anabolic stimulus was nutrient consumption.
Project description:The aim of the study was to investigate how short-term fasting affects whole-body energy homeostasis and skeletal muscle energy/nutrient-sensing pathways and transcriptome in humans. For this purpose, twelve young healthy men were studied during a 24-hour fast. Skeletal muscle biopsies were collected and analyzed at baseline and after 4, 10 and 24h of fasting. As expected, fasting induced a time-dependent decrease in plasma insulin and leptin levels, whereas levels of ketone bodies and free fatty acids increased. This was associated with a metabolic shift from glucose towards lipid oxidation. Transcriptome profiling identified genes that were significantly regulated by fasting in skeletal muscle at both early and late time-points. Collectively, our study provides a comprehensive map of the main energy/nutrient-sensing pathways and transcriptomic changes during short-term adaptation to fasting in human skeletal muscle
Project description:This study seeks to investigate the temporal, genome-wide response of skeletal muscle following cardiotoxin injection within the skeletal muscle of the Astyanax mexicanus – comprised of the river-dwelling surface fish and troglobitic cavefish – providing novel insights into the evolutionary consequence of skeletal muscle regernation.
Project description:Aged skeletal muscle has a diminished capacity to recover after disuse. Although muscle regrowth requires coordinated interactions between immune and progenitor cells, the mechanisms of impaired remodeling in aged skeletal muscle remain poorly understood, yet possibly involving the accumulation of senescent cells. We used a novel flow cytometry approach coupled with scRNAseq to determine the muscle senescent cell identity and transcriptional landscape during skeletal muscle recovery following disuse atrophy. Young and aged mice underwent 14d of hindlimb unloading followed by reloading (7 or 14d). At recovery, old mice showed smaller myofibers and abnormal muscle macrophage dynamics corresponding to greater collagen content. These outcomes coincided with elevated markers of muscle senescence (p21, γH2AX) and increased SPiDER-β-Gal⁺ cells, which inversely correlated with muscle mass. Single-cell resolution of SPiDER+ cells unmasked several senescent interstitial muscle vascular and stromal populations. Senescent interstitial cell populations were enriched in aged muscle and displayed a senescence-associated secretory phenotype (SASP) across multiple stromal, vascular, and immune cell types. Senolytic treatment reduced overall senescent cell burden, attenuated macrophage accumulation, and restored muscle mass and function in aged mice following disuse. These findings identify a multicellular senescence environment within the muscle interstitial niche as a hallmark of impaired muscle recovery following disuse.
Project description:The skeletal muscle interstitial space is the extracellular region around myofibres and mediates crosstalk between resident cell types. We applied a proteomic workflow to characterise the human skeletal muscle interstitial fluid proteome at rest and in response to exercise. Following exhaustive exercise, markers of skeletal muscle damage accumulate in the interstitial space followed in turn by the appearance of immune cell-derived proteins. Among the proteins upregulated after exercise, we identified cathelicidin-related antimicrobial peptide (CAMP) as a bioactive molecule regulating muscle fibre development. Treatment with the bioactive peptide derivative of CAMP (LL-37) resulted in the growth of larger C2C12 skeletal muscle myotubes. Phosphoproteomics revealed that LL-37 activated pathways central to muscle growth and proliferation, including PI3K, AKT, MAPKs, and mTOR. Our findings provide a proof-of-concept that the interstitial fluid proteome can be quantified via microdialysis sampling in vivo. Furthermore, these data highlight the importance of cellular communication in the adaptive response to exercise.
Project description:Systemic administration of β-adrenoceptor (β-AR) agonists has been found to induce skeletal muscle hypertrophy and significant metabolic changes. In the context of energy homeostasis, the importance of β-AR signaling has been highlighted by the inability of β1–3-AR-deficient mice to regulate energy expenditure and susceptibility to diet induced obesity. However, the molecular pathways and gene expression changes that initiate and maintain these phenotypic modulations are poorly understood. Therefore, the aim of this study was to identify differential changes in gene expression in murine skeletal muscle associated with systemic acute administration of the β2-AR agonist formoterol. Skeletal muscle gene expression (from murine tibialis anterior) was profiled at both 1 and 4 hours following systemic administration of the β2-AR agonist formoterol, using 46K Illumina(R) Sentrix BeadArrays. Illumina expression profiling revealed significant expression changes in genes associated with skeletal muscle hypertrophy, myoblast differentiation, metabolism, circadian rhythm, transcription, histones, and oxidative stress.