The rising prevalence of obesity has emerged as a pressing public health concern (1, 2). Obesity that manifests in childhood tends to endure into adulthood, predisposing individuals to cardiovascular and metabolic risks (3), such as dyslipidemia, elevated glucose levels, and high blood pressure. Collectively, these factors contribute to over 30.0% of global mortality (4). Emerging evidence indicates that clusters of cardiometabolic risk (CMR) factors associated with obesity commence early in life, persisting from childhood into adulthood and potentially forecasting future occurrences of diabetes and CMR (5, 6). Investigating the factors associated with CMR during childhood is crucial for implementing proactive management and early-stage interventions.

Cardiorespiratory fitness (CRF), also known as cardiovascular fitness or aerobic fitness, is characterized by the maximum capacity of the cardiovascular and respiratory systems to deliver oxygen to the skeletal muscles during physical activity. As the importance of CRF is now well-established, it was identified as a fundamental indicator in the assessment of health in youth (7). It is widely accepted that higher CRF is beneficial for the prevention of cardiovascular and metabolic diseases in both children and adults (8, 9). Evidence in children demonstrated that even after adjusting for the impact of obesity, the protection effect of CRF on CMR persists (10).

To date, several studies conducted on children and adolescent have consistently demonstrated that fitness, in particularly CRF, is associated with lower CMR, even after accounting for the negative effects of excess body fat (11–15). Notably, boys generally have higher CRF than girls across all age groups (16), and ethnic disparities in CRF have also been highlighted (17). However, to our knowledge, few studies have delved into the sexual dimorphism in this context, and the majority of them have been conducted in Western countries, thus limiting their generalizability. While one study among Chinese children by Shang et.al (13) evaluated CRF through the 50m × 8 shuttle run test and explored its mediation effect, its comparability with other studies remains questionable, and the validity and reliability of this test have not gained widespread acceptance (7). In our study, the 20-m shuttle run test (20mSRT) will be employed, which is more widely used. Furthermore, there remains a gap in understanding the impact of various fatness exposures, how individual markers contribute to CMR as well as the clustered CMR-score, and it is imperative to explore these factors, particularly with regards to sexual differences.

Therefore, this study aims to explore the mediating role of CRF in the association between four fatness indicators and CMR-score with individual CMR markers in Chinese children, and explore sex differences.

To the best of our knowledge, this study is the first to use the 20mSRT to assess CRF and illustrate the extent to which CRF may act as a mediator in the relationship between fatness indicators and CMR in Chinese children. This study revealed that CRF partially attenuate the associations between multiple fatness indicators and individual CMR markers and clustered CMR-score in Chinese children, with the mediation effect size for WHtR and CMR-markers/CMR-score being the largest. Meanwhile, the proportion of mediation were larger in girls, indicating that girls may benefit more from improvements in CRF.

Both obesity and CRF are crucial factors influencing cardiovascular health in childhood. We observed that higher fatness indicators were associated with a worse CMR level, while elevated CRF levels were linked to a better CMR level. These findings align with previous studies (29–32). Childhood obesity is a well-established marker for the clustering of metabolic risk factors, including high triglycerides, low HDL-C, high blood pressure, and dysglycemia (32). Although some therapeutic advances have emerged to address this global problem (33), longitudinal studies with comprehensive data, especially in children with obesity, are still essential to pinpoint the optimal timing for implementing mitigation strategies in children. These studies also suggest that defining a CRF threshold in children may help providers identify those at high risk of cardiometabolic disease, which could be considered in future study.

CRF has been recognized as a predictor of CMR and can be assessed through maximal or submaximal exercise tests. While maximal exercise tests, analyzed for gases, are considered the gold standard, they often require expensive equipment and well-trained staff, which may not always be readily available. In Chinese students aged 7 to 12 years old, the 50m × 8 shuttle run has traditionally been used to assess cardiorespiratory endurance. However, due to its test duration of less than 5 minutes, it may not accurately reflect the actual CRF level. The 20mSRT is currently the most widely used test in school settings worldwide to estimate CRF in children (26). In a review of 73 studies, it demonstrated moderate to high validity against the gold standard for CRF estimation (34). However, it should be concerned that evidence indicated performance in the 20mSRT has a shared variance with body size and fatness (8, 35), which may introduce confounding.

In our study, we observed that the mediation effect size was largest in the associations between one of the fatness indicators “WHtR” and CMR-score and CMR markers. Stoner et. al (14) also found the CRF as mediators in the fatness indicators (BMI, BFMI, and WHtR) and CMR-score in European adolescents (age: 14.1 ± 1.1 years old), the mediation effect sizes were all about 10.0%. Another study from European with children aged 8-11 years also concluded the similar mediation effect, with the fatness evaluated by BMI (15). Our study highlights the largest effect size for WHtR, possibly indicating that abdominal fat may be more important than total body fat, given that WHtR is frequently utilized as a proxy for central adiposity and has been validated as a significant predictor of morbidity (36). In comparison with BMI, WHtR demonstrates a stronger association with cardiovascular disease and provides a more accurate reflection of cardiovascular and metabolic risks (37).

Additionally, we noted that the mediation effect was more pronounced in girls than boys This suggests that interventions aimed at improving CRF may yield greater benefits in girls. In general, girls exhibit higher levels of abdominal fat than boys throughout childhood and adolescence (38). Consequently, improving CRF may potentially lead to easier reduction of abdominal fat in girls. Further research is warranted to investigate the biological mechanisms underlying this gender difference. Our analysis used BMI, BFMI, and WHtR as continuous variables rather than relying on specific clinical cut-offs, which allowed us to examine the dose-response relationships between fatness and CMR, as well as the mediating role of CRF. While our use of continuous variables provides valuable insights, future research could consider the use of clinical cut-offs.

The “fat-but-fit” hypothesis suggests that the risk of all-cause and cardiovascular disease mortality in individuals with obesity but who are fit (i.e., having CRF levels above the age-specific and sex-specific 20th percentile) is not significantly different from that of their normal-weight and fit counterparts (39). Musa et al. (40) found that both fatness and fitness (estimated through the 20mSRT) are independent predictors of blood pressure in Nigerian children. Of these two factors, fatness plays a more important role. Additionally, compared with fat-unfit children, participants with higher CRF had more favorable BP profiles. In our study, we observed that all four fatness indicators (BMI, BMI z score, BFMI and WHtR) partially attenuate the association between fatness and CMR-score in children, with the mediation effect of WHtR being the most substantial, accounting for 12.5%. WHtR is considered an accurate and simpler index for evaluating obesity in children and adolescents (41). To some extent, these findings lend support to the “fat-but-fit” hypothesis. Being fit plays a major role in cardiovascular health, and children benefit from both improved fitness and weight loss. Given that intervention during childhood potentially benefit most, it is critical to conduct relevant intervention studies in children as early as possible in future research.

Several limitations need to be considered of this study. Firstly, we did not estimate the pubertal status of the participants, however, all participant were from grade 3 in primary school with age of 8.5 years, for Chinese children, puberty starts at 9.65 years for boys and 10.65 years for girls (42). Secondly, the cross-sectional design inherently cannot eliminate bidirectional causality, and the narrow age range (8–10 years old) of the participants limit the generalizability, in that large and longitudinal studies may offer more conclusive evidence. Thirdly, there is a concern whether CRF measured by 20mSRT being confounded by body size and composition, but 20mSRT is applicable, convenient and was recommended in large-scale childhood population (43).

In summary, our study results support the promotion that children with excess fatness should pay attention to improving CRF to reduce the harm of fatness to the cardiometabolic system. The more pronounced mediation effect observed in girls suggests potential benefits of CRF interventions. For children and adolescents, addressing both short-term and long-term cardiovascular risks necessitates not only weight management but also the enhancement of cardiopulmonary fitness.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving humans were approved by Ethics Committee of the First Affiliated Hospital of Ningbo University. The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent for participation in this study was provided by the participants’ legal guardians/next of kin.

P-PZ: Data curation, Formal analysis, Investigation, Software, Writing – original draft. Y-XW: Data curation, Formal analysis, Investigation, Methodology, Software, Validation, Writing – original draft. J-YG: Investigation, Methodology, Project administration, Resources, Writing – review & editing. MX: Data curation, Investigation, Supervision, Writing – review & editing. YZ: Data curation, Investigation, Supervision, Writing – review & editing. H-JW: Conceptualization, Resources, Writing – review & editing. PL: Conceptualization, Writing – review & editing. HW: Conceptualization, Data curation, Funding acquisition, Methodology, Resources, Writing – review & editing. LL: Conceptualization, Data curation, Funding acquisition, Investigation, Project administration, Resources, Supervision, Writing – review & editing.