Biology subjects

Norrbom, J.

Publications and source records attributed to Norrbom, J..

6 recordsLinked to original sources

bioRxiv2026

Reduced physiological reserve and a blunted response to acute exercise in adults with cerebral palsy

Cerebral palsy (CP) is an early-onset neurodevelopmental condition associated with metabolic impairment and an increased risk of non-communicable diseases across the lifespan. However, the basis of these changes remains largely unknown. This study provides a comprehensive cardiometabolic and physical function profile of 23 adults with CP relative to 33 typically developing (TD) adolescents and 61 TD adults. Compared to TD individuals, adults with CP exhibited reduced cardiorespiratory fitness, smaller cardiac dimensions, and lower muscle mass. Circulating metabolomic and proteomic profiling identified a distinct molecular signature in CP, including altered tricarboxylic acid (TCA) cycle metabolites, and elevated myostatin, matrix-related proteins and pro-inflammatory cytokines. We further tested the capacity for physiological and molecular adaptation using an acute bout of endurance exercise. In response to exercise, individuals with CP exhibited an attenuated response compared to TD groups, characterized by a blunted lactate response and lower venous oxygen levels. TD participants also increased canonical exercise-responsive factors, including NADK, IL-8, ANGPTL1 and GDF15, whereas these responses were attenuated in CP. These novel findings define a distinct cardiometabolic profile in adults with CP at rest and reveal an attenuated molecular response to exercise. These data carry implications for targeted interventions and prevention strategies across the lifespan.

physiology↗

bioRxiv2025

Transcriptomic Profiling of scWAT Reveals Reduced Lipid-Associated Macrophage Signatures in Long-Term Endurance- and Resistance-Trained Athletes

Regular exercise training is associated with systemic and tissue-specific performance and health benefits, yet long-term molecular adaptations in subcutaneous abdominal white adipose tissue (scWAT) remain unclear. We analyzed the resting scWAT transcriptome of 89 adults (35-50 years) who were long-term (>15 years) endurance- or strength-trained, or untrained. Long-term training was linked to enrichment of ribosomal, mitochondrial, and aerobic metabolism-related pathways, while immune-related pathways were enriched in untrained individuals. A distinct sex dimorphic scWAT was identified: untrained females exhibited a more metabolically favorable, trained-like transcriptomic profile, and untrained males an untrained-like profile. In trained males, the inflammatory gene signature was lower than in untrained males. We also identified 11 genes specific to lipid-associated macrophages with lower expression in trained individuals, particularly in all endurance-trained individuals and strength-trained females. These findings highlight sex-specific, exercise-induced adaptations in scWAT relevant to metabolic health, and underscore the importance of including both sexes in scWAT research.

physiology↗

bioRxiv2024

Endurance Exercise Elevates Plasma Mature Brain-Derived Neurotrophic Factor through Child- and Adulthood, with Amplified Effects in Adults

BackgroundBrain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a central role in neuronal health. BDNF exists in two primary isoforms, the mature form (mBDNF) and its precursor (proBDNF), with opposing downstream effects on neuronal function. The positive effect of exercise on plasma levels of the BDNF-isoforms has been extensively studied in adults. However, equivalent investigations are lacking in children and youth. MethodsTwenty healthy children (9-12 years old), 19 adolescents (13-17 years old), and 39 adults (23-49 years old) donated venous blood before and after a 45-minute run. Platelet-poor plasma was analyzed for pro- and mBDNF using enzyme-linked immunosorbent assay. Maximal oxygen uptake and anthropometric data were assessed in all participants, while Tanner stage, circulating sex hormones, and accelerometry-based activity level were assessed in children and adolescents. ResultsWe found that children, adolescents, and adults have similar basal levels of pro-(337-543 pg x ml-1) and mBDNF (650-1111 pg x ml-1). For children and adolescents, basal levels of mBDNF correlated with average time spent in vigorous activity (r=0.5794, p=0.0015). In response to acute endurance exercise, mBDNF increased by 701 {+/-} 946, 1232 {+/-} 1105, and 1557 {+/-} 1168 pg x ml-1 in children, adolescents, and adults, respectively. The acute endurance exercise did not affect proBDNF levels (p>0.05). ConclusionOur results demonstrate that basal plasma pro- and mBDNF levels do not depend on age and maturity. Plasma mBDNF levels increase following endurance exercise in all age groups, but to a greater extent in adults. Highlights/ImpactO_LIWe show that in children and adolescents, regular vigorous physical activity is key to increased basal levels of plasma mBDNF, a factor linked to neuroplasticity and brain health. C_LIO_LIThe ability to elevate mBDNF through exercise is present across all age groups, with the greatest increase in adults. C_LIO_LIThe mBDNF response to physical exercise seems to be independent of underlying physical fitness. C_LIO_LIOur findings suggest that basal plasma mBDNF levels may reflect the cumulative effects of repeated exercise rather than an individuals overall physical fitness. C_LI

physiology↗

bioRxiv2024

The 24-Hour Time Course of Integrated Molecular Responses to Resistance Exercise in Human Skeletal Muscle Implicates MYC as a Hypertrophic Regulator That is Sufficient for Growth

Molecular control of recovery after exercise in muscle is temporally dynamic. A time course of biopsies around resistance exercise (RE) combined with -omics is necessary to better comprehend the molecular contributions of skeletal muscle adaptation in humans. Vastus lateralis biopsies before and 30 minutes, 3-, 8-, and 24-hours after acute RE were collected. A time-point matched biopsy-only group was also included. RNA-sequencing defined the transcriptome while DNA methylomics and computational approaches complemented these data. The post-RE time course revealed: 1) DNA methylome responses at 30 minutes corresponded to upregulated genes at 3 hours, 2) a burst of translation- and transcription-initiation factor-coding transcripts occurred between 3 and 8 hours, 3) global gene expression peaked at 8 hours, 4) ribosome-related genes dominated the mRNA landscape between 8 and 24 hours, 5) methylation-regulated MYC was a highly influential transcription factor throughout the 24-hour recovery and played a primary role in ribosome-related mRNA levels between 8 and 24 hours. The influence of MYC in human muscle adaptation was strengthened by transcriptome information from acute MYC overexpression in mouse muscle. To test whether MYC was sufficient for hypertrophy, we generated a muscle fiber-specific doxycycline inducible model of pulsatile MYC induction. Periodic 48-hour pulses of MYC over 4 weeks resulted in higher muscle mass and fiber size in the soleus of adult female mice. Collectively, we present a temporally resolved resource for understanding molecular adaptations to RE in muscle and reveal MYC as a regulator of RE-induced mRNA levels and hypertrophy.

cell biology↗

bioRxiv2020

Genetic and Epigenetic Regulation of Skeletal Muscle Ribosome Biogenesis with Exercise

Ribosomes are the macromolecular engines of protein synthesis. Skeletal muscle ribosome biogenesis is stimulated by exercise, but the contribution of ribosomal DNA (rDNA) copy number and methylation to exercise-induced rDNA transcription is unclear. To investigate the genetic and epigenetic regulation of ribosome biogenesis with exercise, a time course of skeletal muscle biopsies was obtained from 30 participants (18 men and 12 women; 31 {+/-}8 yrs, 25 {+/-}4 kg/m2) at rest and 30 min, 3h, 8h, and 24h after acute endurance (n=10, 45 min cycling, 70% VO2max) or resistance exercise (n=10, 4 x 7 x 2 exercises); 10 control participants underwent biopsies without exercise. rDNA transcription and dosage were assessed using qPCR and whole genome sequencing. rDNA promoter methylation was investigated using massARRAY EpiTYPER, and global rDNA CpG methylation was assessed using reduced-representation bisulfite sequencing. Ribosome biogenesis and MYC transcription were associated with resistance but not endurance exercise, indicating preferential up-regulation during hypertrophic processes. With resistance exercise, ribosome biogenesis was associated with rDNA gene dosage as well as epigenetic changes in enhancer and non-canonical MYC-associated areas in rDNA, but not the promoter. A mouse model of in vivo metabolic RNA labeling and genetic myonuclear fluorescent labeling validated the effects of an acute hypertrophic stimulus on ribosome biogenesis and Myc transcription, and corroborated rDNA enhancer and Myc-associated methylation alterations specifically in myonuclei. This study provides the first information on skeletal muscle genetic and rDNA gene-wide epigenetic regulation of ribosome biogenesis in response to exercise, revealing novel roles for rDNA dosage and CpG methylation. GRAPHICAL ABSTRACT O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

cell biology↗

bioRxiv2019

Differential response trajectories to acute exercise in blood and muscle

A physically active lifestyle is essential for maintaining health, and is a powerful way to prevent chronic disease. However, the molecular mechanisms that drive exercise adaptation and transduce its beneficial effects, are incompletely understood. Here, we combined data from 49 studies that measured the whole transcriptome in humans before and after exercise to provide the power to draw novel observations not seen in any individual study alone. The resulting curated and standardized resource includes samples from skeletal muscle (n=1,260) and blood (n=726) in response to endurance or resistance exercise and training. Using a linear mixed effects meta-regression model selection strategy, we detected specific time patterns and novel regulatory modulators of the acute exercise response. Acute and long term responses to exercise were transcriptionally distinct. Exercise induced a more pronounced inflammatory response in skeletal muscle of older individuals. We identified multiple sex-specific response genes, where MTMR3 is a novel exercise-regulated gene. These results deepen our understanding of the transcriptional responses to exercise and provide a powerful resource for future research efforts in exercise physiology and medicine.

physiology↗