Genetic Associations With Acceleration, Change of Direction, Jump Height, and Speed in English Academy Football Players.

ABSTRACT: McAuley, ABT, Hughes, DC, Tsaprouni, LG, Varley, I, Suraci, B, Bradley, B, Baker, J, Herbert, AJ, and Kelly, AL. Genetic associations with acceleration, change of direction, jump height, and speed in English academy football players. J Strength Cond Res 38(2): 350-359, 2024-High-intensity movements and explosive actions are commonly assessed during athlete development in football (soccer). Although many environmental factors underpin these power-orientated traits, research suggests that there is also a sizeable genetic component. Therefore, this study examined the association of 22 single-nucleotide polymorphisms (SNPs) with acceleration, change of direction, jump height, and speed in academy football players. One hundred and forty-nine, male, under-12 to under-23 football players from 4 English academies were examined. Subjects performed 5-, 10-, 20-, and 30-m sprints, countermovement jumps (CMJs), and the 5-0-5 agility test. Simple linear regression was used to analyze individual SNP associations, whereas both unweighted and weighted total genotype scores (TGS; TWGS) were computed to measure the combined influence of all SNPs. To control for multiple testing, a Benjamini-Hochberg false discovery rate of 0.05 was applied to all genotype model comparisons. In isolation, the GALNT13 (rs10196189) G allele and IL6 (rs1800795) G/G genotype were associated with faster (∼4%) 5-, 10-, and 20-m sprints and higher (∼16%) CMJs, respectively (p < 0.001). Furthermore, the TGS and TWGS significantly correlated with all performance assessments, explaining between 6 and 33% of the variance (p < 0.001). This study demonstrates that some genetic variants are associated with power-orientated phenotypes in youth football players and may add value toward a future polygenic profile of physical performance.

Uncovering the mechanisms of MuRF1-induced ubiquitylation and revealing similarities with MuRF2 and MuRF3.

MuRF1 (Muscle-specific RING finger protein 1; gene name TRIM63) is a ubiquitin E3 ligase, associated with the progression of muscle atrophy. As a RING (Really Interesting New Gene) type E3 ligase, its unique activity of ubiquitylation is driven by a specific interaction with a UBE2 (ubiquitin conjugating enzyme). Our understanding of MuRF1 function remains unclear as candidate UBE2s have not been fully elucidated. In the present study, we screened human ubiquitin dependent UBE2s in vitro and found that MuRF1 engages in ubiquitylation with UBE2D, UBE2E, UBE2N/V families and UBE2W. MuRF1 can cause mono-ubiquitylation, K48- and K63-linked polyubiquitin chains in a UBE2 dependent manner. Moreover, we identified a two-step UBE2 dependent mechanism whereby MuRF1 is monoubiquitylated by UBE2W which acts as an anchor for UBE2N/V to generate polyubiquitin chains. With the in vitro ubiquitylation assay, we also found that MuRF2 and MuRF3 not only share the same UBE2 partners as MuRF1 but can also directly ubiquitylate the same substrates: Titin (A168-A170), Desmin, and MYLPF (Myosin Light Chain, Phosphorylatable, Fast Skeletal Muscle; also called Myosin Light Regulatory Chain 2). In summary, our work presents new insights into the mechanisms that underpin MuRF1 activity and reveals overlap in MuRF-induced ubiquitylation which could explain their partial redundancy in vivo.

A critical discussion on the relationship between E3 ubiquitin ligases, protein degradation, and skeletal muscle wasting: it's not that simple.

Ubiquitination is an important post-translational modification (PTM) for protein substrates, whereby ubiquitin is added to proteins through the coordinated activity of activating (E1), ubiquitin-conjugating (E2), and ubiquitin ligase (E3) enzymes. The E3s provide key functions in the recognition of specific protein substrates to be ubiquitinated and aid in determining their proteolytic or nonproteolytic fates, which has led to their study as indicators of altered cellular processes. MuRF1 and MAFbx/Atrogin-1 were two of the first E3 ubiquitin ligases identified as being upregulated in a range of different skeletal muscle atrophy models. Since their discovery, the expression of these E3 ubiquitin ligases has often been studied as a surrogate measure of changes to bulk protein degradation rates. However, emerging evidence has highlighted the dynamic and complex regulation of the ubiquitin proteasome system (UPS) in skeletal muscle and demonstrated that protein ubiquitination is not necessarily equivalent to protein degradation. These observations highlight the potential challenges of quantifying E3 ubiquitin ligases as markers of protein degradation rates or ubiquitin proteasome system (UPS) activation. This perspective examines the usefulness of monitoring E3 ubiquitin ligases for determining specific or bulk protein degradation rates in the settings of skeletal muscle atrophy. Specific questions that remain unanswered within the skeletal muscle atrophy field are also identified, to encourage the pursuit of new research that will be critical in moving forward our understanding of the molecular mechanisms that govern protein function and degradation in muscle.

Genetic associations with technical capabilities in English academy football players: a preliminary study.

BACKGROUND: Technical capabilities have significant discriminative and prognostic power in youth football. Although, many factors influence technical performance, no research has explored the genetic contribution. As such, the purpose of this study was to examine the association of several single nucleotide polymorphisms (SNPs) with technical assessments in youth football players. METHODS: Fifty-three male under-13 to under-18 outfield football players from two Category 3 English academies were genotyped for eight SNPs. Objective and subjective technical performance scores in dribbling, passing, and shooting were collated. Simple linear regression was used to analyse individual SNP associations each variable, whereas both unweighted and weighted total genotype scores (TGSs; TWGSs) were computed to measure the combined influence of all SNPs. RESULTS: In isolation, the ADBR2 (rs1042714) C allele, BDNF (rs6265) C/C genotype, DBH (rs1611115) C/C genotype, and DRD1 (rs4532) C allele were associated with superior (8-10%) objective dribbling and/or shooting performance. The TGSs and/or TWGSs were significantly correlated with each technical assessment (except subjective passing), explaining up to 36% and 40% of the variance in the objective and subjective assessments, respectively. CONCLUSIONS: The results of this study suggest inter-individual genetic variation may influence the technical capabilities of youth football players and proposes several candidate SNPs that warrant further investigation.

Genetic Variations between Youth and Professional Development Phase English Academy Football Players.

The purpose of this study was to examine differences in the genotype frequency distribution of thirty-three single nucleotide variants (SNVs) between youth development phase (YDP) and professional development phase (PDP) academy football players. One hundred and sixty-six male football players from two Category 1 and Category 3 English academies were examined within their specific age phase: YDP (n = 92; aged 13.84 ± 1.63 years) and PDP (n = 74; aged 18.09 ± 1.51 years). Fisher's exact tests were used to compare individual genotype frequencies, whereas unweighted and weighted total genotype scores (TGS; TWGS) were computed to assess differences in polygenic profiles. In isolation, the IL6 (rs1800795) G allele was overrepresented in PDP players (90.5%) compared to YDP players (77.2%; p = 0.023), whereby PDP players had nearly three times the odds of possessing a G allele (OR = 2.83, 95% CI: 1.13-7.09). The TGS (p = 0.001) and TWGS (p < 0.001) were significant, but poor, in distinguishing YDP and PDP players (AUC = 0.643-0.694), with PDP players exhibiting an overall more power-orientated polygenic profile. If validated in larger independent youth football cohorts, these findings may have important implications for future studies examining genetic associations in youth football.

Ubiquitin Ligases in Longevity and Aging Skeletal Muscle.

The development and prevalence of diseases associated with aging presents a global health burden on society. One hallmark of aging is the loss of proteostasis which is caused in part by alterations to the ubiquitin-proteasome system (UPS) and lysosome-autophagy system leading to impaired function and maintenance of mass in tissues such as skeletal muscle. In the instance of skeletal muscle, the impairment of function occurs early in the aging process and is dependent on proteostatic mechanisms. The UPS plays a pivotal role in degradation of misfolded and aggregated proteins. For the purpose of this review, we will discuss the role of the UPS system in the context of age-related loss of muscle mass and function. We highlight the significant role that E3 ubiquitin ligases play in the turnover of key components (e.g., mitochondria and neuromuscular junction) essential to skeletal muscle function and the influence of aging. In addition, we will briefly discuss the contribution of the UPS system to lifespan. By understanding the UPS system as part of the proteostasis network in age-related diseases and disorders such as sarcopenia, new discoveries can be made and new interventions can be developed which will preserve muscle function and maintain quality of life with advancing age.

CORP: Gene delivery into murine skeletal muscle using in vivo electroporation.

The strategy of gene delivery into skeletal muscles has provided exciting avenues in identifying new potential therapeutics toward muscular disorders and addressing basic research questions in muscle physiology through overexpression and knockdown studies. In vivo electroporation methodology offers a simple, rapidly effective technique for the delivery of plasmid DNA into postmitotic skeletal muscle fibers and the ability to easily explore the molecular mechanisms of skeletal muscle plasticity. The purpose of this review is to describe how to robustly electroporate plasmid DNA into different hindlimb muscles of rodent models. Furthermore, key parameters (e.g., voltage, hyaluronidase, and plasmid concentration) that contribute to the successful introduction of plasmid DNA into skeletal muscle fibers will be discussed. In addition, details on processing tissue for immunohistochemistry and fiber cross-sectional area (CSA) analysis will be outlined. The overall goal of this review is to provide the basic and necessary information needed for successful implementation of in vivo electroporation of plasmid DNA and thus open new avenues of discovery research in skeletal muscle physiology.

SnapShot: Skeletal muscle atrophy.

Skeletal muscle size is highly plastic and sensitive to a variety of stimuli. Muscle atrophy occurs as the result of changes in multiple signaling pathways that regulate both protein synthesis and degradation. The signaling pathways that are activated or inhibited depend on the specific stimuli that are altered. To view this SnapShot, open of download the PDF.

Activation of Crtc2/Creb1 in skeletal muscle enhances weight loss during intermittent fasting.

The Creb-Regulated Transcriptional Coactivator (Crtc) family of transcriptional coregulators drive Creb1-mediated transcription effects on metabolism in many tissues, but the in vivo effects of Crtc2/Creb1 transcription on skeletal muscle metabolism are not known. Skeletal muscle-specific overexpression of Crtc2 (Crtc2 mice) induced greater mitochondrial activity, metabolic flux capacity for both carbohydrates and fats, improved glucose tolerance and insulin sensitivity, and increased oxidative capacity, supported by upregulation of key metabolic genes. Crtc2 overexpression led to greater weight loss during alternate day fasting (ADF), selective loss of fat rather than lean mass, maintenance of higher energy expenditure during the fast and reduced binge-eating during the feeding period. ADF downregulated most of the mitochondrial electron transport genes, and other regulators of mitochondrial function, that were substantially reversed by Crtc2-driven transcription. Glucocorticoids acted with AMPK to drive atrophy and mitophagy, which was reversed by Crtc2/Creb1 signaling. Crtc2/Creb1-mediated signaling coordinates metabolic adaptations in skeletal muscle that explain how Crtc2/Creb1 regulates metabolism and weight loss.

Identification of the MuRF1 Skeletal Muscle Ubiquitylome Through Quantitative Proteomics.

MuRF1 (TRIM63) is a muscle-specific E3 ubiquitin ligase and component of the ubiquitin proteasome system. MuRF1 is transcriptionally upregulated under conditions that cause muscle loss, in both rodents and humans, and is a recognized marker of muscle atrophy. In this study, we used in vivo electroporation to determine whether MuRF1 overexpression alone can cause muscle atrophy and, in combination with ubiquitin proteomics, identify the endogenous MuRF1 substrates in skeletal muscle. Overexpression of MuRF1 in adult mice increases ubiquitination of myofibrillar and sarcoplasmic proteins, increases expression of genes associated with neuromuscular junction instability, and causes muscle atrophy. A total of 169 ubiquitination sites on 56 proteins were found to be regulated by MuRF1. MuRF1-mediated ubiquitination targeted both thick and thin filament contractile proteins, as well as, glycolytic enzymes, deubiquitinases, p62, and VCP. These data reveal a potential role for MuRF1 in not only the breakdown of the sarcomere but also the regulation of metabolism and other proteolytic pathways in skeletal muscle.

The ketogenic diet preserves skeletal muscle with aging in mice.

The causes of the decline in skeletal muscle mass and function with age, known as sarcopenia, are poorly understood. Nutrition (calorie restriction) interventions impact many cellular processes and increase lifespan and preserve muscle mass and function with age. As we previously observed an increase in life span and muscle function in aging mice on a ketogenic diet (KD), we aimed to investigate the effect of a KD on the maintenance of skeletal muscle mass with age and the potential molecular mechanisms of this action. Twelve-month-old mice were assigned to an isocaloric control or KD until 16 or 26 months of age, at which time skeletal muscle was collected for evaluating mass, morphology, and biochemical properties. Skeletal muscle mass was significantly greater at 26 months in the gastrocnemius of mice on the KD. This result in KD mice was associated with a shift in fiber type from type IIb to IIa fibers and a range of molecular parameters including increased markers of NMJ remodeling, mitochondrial biogenesis, oxidative metabolism, and antioxidant capacity, while decreasing endoplasmic reticulum (ER) stress, protein synthesis, and proteasome activity. Overall, this study shows the effectiveness of a long-term KD in mitigating sarcopenia. The diet preferentially preserved oxidative muscle fibers and improved mitochondrial and antioxidant capacity. These adaptations may result in a healthier cellular environment, decreasing oxidative and ER stress resulting in less protein turnover. These shifts allow mice to better maintain muscle mass and function with age.

Genetic association research in football: A systematic review.

Genetic variation is responsible for a large amount of the inter-individual performance disparities seen in sport. As such, in the last ten years genetic association studies have become more common; with one of the most frequently researched sports being football. However, the progress and methodological rigour of genetic association research in football is yet to be evaluated. Therefore, the aim of this paper was to identify and evaluate all genetic association studies involving football players and outline where and how future research should be directed. Firstly, a systematic search was conducted in the Pubmed and SPORTDiscus databases, which identified 80 eligible studies. Progression analysis revealed that 103 distinct genes have been investigated across multiple disciplines; however, research has predominately focused on the association of the ACTN3 or ACE gene. Furthermore, 55% of the total studies have been published within the last four years; showcasing that genetic association research in football is increasing at a substantial rate. However, there are several methodological inconsistencies which hinder research implications, such as; inadequate description or omission of ethnicity and on-field positions. Furthermore, there is a limited amount of research on several key areas crucial to footballing performance, in particular; psychological related traits. Moving forward, improved research designs, larger sample sizes, and the utilisation of genome-wide and polygenic profiling approaches are recommended. Finally, we introduce the Football Gene Project, which aims to address several of these limitations and ultimately facilitate greater individualised athlete development within football.

Knockdown of the E3 ubiquitin ligase UBR5 and its role in skeletal muscle anabolism.

UBR5 is an E3 ubiquitin ligase positively associated with anabolism, hypertrophy, and recovery from atrophy in skeletal muscle. The precise mechanisms underpinning UBR5's role in the regulation of skeletal muscle mass remain unknown. The present study aimed to elucidate these mechanisms by silencing the UBR5 gene in vivo. To achieve this aim, we electroporated a UBR5-RNAi plasmid into mouse tibialis anterior muscle to investigate the impact of reduced UBR5 on anabolic signaling MEK/ERK/p90RSK and Akt/GSK3ß/p70S6K/4E-BP1/rpS6 pathways. Seven days after UBR5 RNAi electroporation, although reductions in overall muscle mass were not detected, the mean cross-sectional area (CSA) of green fluorescent protein (GFP)-positive fibers were reduced (-9.5%) and the number of large fibers were lower versus the control. Importantly, UBR5-RNAi significantly reduced total RNA, muscle protein synthesis, ERK1/2, Akt, and GSK3ß activity. Although p90RSK phosphorylation significantly increased, total p90RSK protein levels demonstrated a 45% reduction with UBR5-RNAi. Finally, these early events after 7 days of UBR5 knockdown culminated in significant reductions in muscle mass (-4.6%) and larger reductions in fiber CSA (-18.5%) after 30 days. This was associated with increased levels of phosphatase PP2Ac and inappropriate chronic elevation of p70S6K and rpS6 between 7 and 30 days, as well as corresponding reductions in eIF4e. This study demonstrates that UBR5 plays an important role in anabolism/hypertrophy, whereby knockdown of UBR5 culminates in skeletal muscle atrophy.

The association of the ACTN3 R577X and ACE I/D polymorphisms with athlete status in football: a systematic review and meta-analysis.

The aim of this review was to assess the association of ACTN3 R577X and ACE I/D polymorphisms with athlete status in football and determine which allele and/or genotypes are most likely to influence this phenotype via a meta-analysis. A comprehensive search identified 17 ACTN3 and 19 ACE studies. Significant associations were shown between the presence of the ACTN3 R allele and professional footballer status (OR = 1.35, 95% CI: 1.18-1.53) and the ACE D allele and youth footballers (OR = 1.18, 95% CI: 1.01-1.38). More specifically, the ACTN3 RR genotype (OR = 1.48, 95% CI: 1.23-1.77) and ACE DD genotype (OR = 1.29, 95% CI: 1.02-1.63) exhibited the strongest associations, respectively. These findings may be explained by the association of the ACTN3 RR genotype and ACE DD genotype with power-orientated phenotypes and the relative contribution of power-orientated phenotypes to success in football. As such, the results of this review provide further evidence that individual genetic variation may contribute towards athlete status and can differentiate athletes of different competitive playing statuses in a homogenous team-sport cohort. Moreover, the ACTN3 R577X and ACE I/D polymorphisms are likely (albeit relatively minor) contributing factors that influence athlete status in football.

Identification and characterization of Fbxl22, a novel skeletal muscle atrophy-promoting E3 ubiquitin ligase.

Muscle-specific E3 ubiquitin ligases have been identified in muscle atrophy-inducing conditions. The purpose of the current study was to explore the functional role of F-box and leucine-rich protein 22 (Fbxl22), and a newly identified splice variant (Fbxl22-193), in skeletal muscle homeostasis and neurogenic muscle atrophy. In mouse C2C12 muscle cells, promoter fragments of the Fbxl22 gene were cloned and fused with the secreted alkaline phosphatase reporter gene to assess the transcriptional regulation of Fbxl22. The tibialis anterior muscles of male C57/BL6 mice (12-16 wk old) were electroporated with expression plasmids containing the cDNA of two Fbxl22 splice variants and tissues collected after 7, 14, and 28 days. Gastrocnemius muscles of wild-type and muscle-specific RING finger 1 knockout (MuRF1 KO) mice were electroporated with an Fbxl22 RNAi or empty plasmid and denervated 3 days posttransfection, and tissues were collected 7 days postdenervation. The full-length gene and novel splice variant are transcriptionally induced early (after 3 days) during neurogenic muscle atrophy. In vivo overexpression of Fbxl22 isoforms in mouse skeletal muscle leads to evidence of myopathy/atrophy, suggesting that both are involved in the process of neurogenic muscle atrophy. Knockdown of Fbxl22 in the muscles of MuRF1 KO mice resulted in significant additive muscle sparing 7 days after denervation. Targeting two E3 ubiquitin ligases appears to have a strong additive effect on protecting muscle mass loss with denervation, and these findings have important implications in the development of therapeutic strategies to treat muscle atrophy.

Genomewide Association Study of Acute Anterior Uveitis Identifies New Susceptibility Loci.

Purpose: Acute anterior uveitis (AAU) is a common intraocular inflammatory disease. AAU occurs in 30% to 50% of patients with ankylosing spondylitis (AS), and both conditions are strongly associated with human leukocyte antigen (HLA)-B27, implying a shared etiology. This study aims to apply genomewide association study (GWAS) to characterize the genetic associations of AAU and their relationship to the genetics of AS. Methods: We undertook the GWAS analyses in 2752 patients with AS with AAU (cases) and 3836 patients with AS without AAU (controls). There were 7,436,415 single-nucleotide polymorphisms (SNPs) available after SNP microarray genotyping, imputation, and quality-control filtering. Results: We identified one locus associated with AAU at genomewide significance: rs9378248 (P = 2.69 × 10-8, odds ratio [OR] = 0.78), lying close to HLA-B. Suggestive association was observed at 11 additional loci, including previously reported AS loci ERAP1 (rs27529, P = 2.19 × 10-7, OR = 1.22) and NOS2 (rs2274894, P = 8.22 × 10-7, OR = 0.83). Multiple novel suggestive associations were also identified, including MERTK (rs10171979, P = 2.56 × 10-6, OR = 1.20), KIFAP3 (rs508063, P = 5.64 × 10-7, OR = 1.20), CLCN7 (rs67412457, P = 1.33 × 10-6, OR = 1.25), ACAA2 (rs9947182, P = 9.70 × 10-7, OR = 1.37), and 5 intergenic loci. The SNP-based heritability is approximately 0.5 for AS alone, and is much higher (approximately 0.7) for AS with AAU. Consistent with the high heritability, a genomewide polygenic risk score shows strong power in identifying individuals at high risk of either AS with AAU or AS alone. Conclusions: We report here the first GWAS for AAU and identify new susceptibility loci. Our findings confirm the strong overlap in etiopathogenesis of AAU with AS, and also provide new insights into the genetic basis of AAU.

UBR5 is a novel E3 ubiquitin ligase involved in skeletal muscle hypertrophy and recovery from atrophy.

KEY POINTS: We have recently identified that a HECT domain E3 ubiquitin ligase, named UBR5, is altered epigenetically (via DNA methylation) after human skeletal muscle hypertrophy, where its gene expression is positively correlated with increasing lean leg mass after training and retraining. In the present study we extensively investigate this novel and uncharacterised E3 ubiquitin ligase (UBR5) in skeletal muscle atrophy, recovery from atrophy and injury, anabolism and hypertrophy. We demonstrated that UBR5 was epigenetically altered via DNA methylation during recovery from atrophy. We also determined that UBR5 was alternatively regulated versus well characterised E3 ligases, MuRF1/MAFbx, at the gene expression level during atrophy, recovery from atrophy and hypertrophy. UBR5 also increased at the protein level during recovery from atrophy and injury, hypertrophy and during human muscle cell differentiation. Finally, in humans, genetic variations of the UBR5 gene were strongly associated with larger fast-twitch muscle fibres and strength/power performance versus endurance/untrained phenotypes. ABSTRACT: We aimed to investigate a novel and uncharacterized E3 ubiquitin ligase in skeletal muscle atrophy, recovery from atrophy/injury, anabolism and hypertrophy. We demonstrated an alternate gene expression profile for UBR5 vs. well characterized E3-ligases, MuRF1/MAFbx, where, after atrophy evoked by continuous-low-frequency electrical-stimulation in rats, MuRF1/MAFbx were both elevated, yet UBR5 was unchanged. Furthermore, after recovery of muscle mass post TTX-induced atrophy in rats, UBR5 was hypomethylated and increased at the gene expression level, whereas a suppression of MuRF1/MAFbx was observed. At the protein level, we also demonstrated a significant increase in UBR5 after recovery of muscle mass from hindlimb unloading in both adult and aged rats, as well as after recovery from atrophy evoked by nerve crush injury in mice. During anabolism and hypertrophy, UBR5 gene expression increased following acute loading in three-dimensional bioengineered mouse muscle in vitro, and after chronic electrical stimulation-induced hypertrophy in rats in vivo, without increases in MuRF1/MAFbx. Additionally, UBR5 protein abundance increased following functional overload-induced hypertrophy of the plantaris muscle in mice and during differentiation of primary human muscle cells. Finally, in humans, genetic association studies (>700,000 single nucleotide polymorphisms) demonstrated that the A alleles of rs10505025 and rs4734621 single nucleotide polymorphisms in the UBR5 gene were strongly associated with larger cross-sectional area of fast-twitch muscle fibres and favoured strength/power vs. endurance/untrained phenotypes. Overall, we suggest that: (i) UBR5 comprises a novel E3 ubiquitin ligase that is inversely regulated to MuRF1/MAFbx; (ii) UBR5 is epigenetically regulated; and (iii) UBR5 is elevated at both the gene expression and protein level during recovery from skeletal muscle atrophy and hypertrophy.

A profile of health, lifestyle and training habits of 4720 Australian recreational runners-The case for promoting running for health benefits.

ISSUE ADDRESSED: The aim of this study was to characterise lifestyle and training habits of a large cohort of Australian recreational runners. Understanding the health benefits of recreational running and differentiating between the habits of males and females may allow for the development of gender-specific messaging for promoting recreational running as a form of physical activity. METHODS: An online questionnaire was used to collect data from 4720 Australian recreational runners. Data on physical, lifestyle and training characteristics of male and female subgroups were compared using chi-square tests. Multiple logistic regression method was used to assess the effect of running experience on the reported clinically significant weight loss. RESULTS: The study cohort was 54.1% female and 45.9% male. Smoking was uncommon among surveyed runners. The most typical weekly running distance in the cohort was 20-40 km, usually distributed by 2-5 running sessions. Significantly more males than females reported running over 40 km per week (29.9% vs 18.9%, P < .001) and running at least six sessions per week (11.5% vs 6.7%, P < .001). The majority (72.9%) of runners had normal BMI, and the cohort reported a lower overweight/obesity rate than the Australian population. The logistic regression model indicated that commencing running may lead to a clinically significant weight loss irrespectively of sex, participation in other sports and injury history. CONCLUSION: Recreational running was associated with beneficial health outcomes. Commencement of running is associated with weight loss, and regular running supports healthy weight maintenance. Male and female runners had different running preferences which should be taken into account for physical activity promotion. SO WHAT?: Captured health outcomes associated with running and described sex differences in training patterns may assist in development of physical activity promotion programmes involving recreational running, particularly targeting weight loss and healthy weight maintenance.