Cardiovascular diseases (CVD) are the leading cause of death globally and constitute a major public health challenge. They not only compromise individuals’ health and shorten lifespan, but also substantially reduce patients’ quality of life. In addition, they place a significant burden on global healthcare systems due to the high medical costs associated with their management [1]. The CVD burden is particularly severe in China, where it has consistently remained the leading cause of death among both urban and rural residents. By 2023, the number of CVD patients in China was estimated to reach 330 million, with no indication of a turning point in the growing disease burden [2]. Obesity, being one of the key pathogenic risk factors for CVD, can directly drive its onset and progression through metabolic and inflammatory pathways [3]. However, the current global prevalence of obesity is alarming: in 2021, approximately 211 million adults aged 25 and above were overweight or obese, accounting for nearly half of the global adult population [4]. Moreover, the issue of obesity among Chinese college students is becoming increasingly prominent and showing a continuous upward trend [5, 6].

Aerobic training, which focuses on aerobic metabolism, has been widely validated as an effective intervention for enhancing cardiorespiratory function, improving metabolic indicators, and reducing the risk of chronic diseases such as obesity and CVD [7, 8]. It has been established as a crucial measure for the primary prevention of CVD [9]. To maximize the fat-reducing effects of aerobic training, Jeukendrup and Achten [10] introduced the concept of “maximal fat oxidation (FATmax)-intensity” in 2001. This refers to the individualized exercise intensity corresponding to the peak rate of fat oxidation that occurs during a given time period [10]. FATmax training typically involves low to moderate exercise intensity efficiently mobilizing fat for energy, promoting fat reduction while preserving lean body mass, thereby effectively improving body composition, making it particularly suitable for overweight and obese populations [11, 12, 13].

In summary, given the high incidence and growing burden of CVD, the rising prevalence of obesity among college students, and the clear potential of FATmax training in improving cardiovascular health, this study aims to thoroughly investigate the relationship between FATmax-intensity training, obesity, and cardiovascular health outcomes. It will also explore the underlying mechanisms, providing a scientific basis for more precise and effective strategies for the prevention and intervention of CVD.

This study presents evidence that a 12-week FATmax-intensity exercise training intervention can improve body composition, enhance cardiorespiratory function, and reduce CVD risk in college students. The significant improvements observed in various indicators suggest that this training model has potential protective effects on cardiovascular health within the population.

Notably, the study documented significant reductions in body weight, fat mass, and WHR (all p 0.05), indicating effective improvements in disordered lipid metabolism, a crucial factor in lowering the risk of CVD onset [16, 17]. An elevated WHR signifies excessive abdominal fat accumulation, which possesses active endocrine functions and secretes pro-inflammatory cytokines and other harmful hormones [18]. These bioactive substances are known to induce vascular endothelial dysfunction and increase inflammatory responses, which in turn promote the development of atherosclerosis and rising CVD risk. Furthermore, a high WHR is often closely associated with metabolic syndrome, a condition that also contributes to an increased risk of CVD [19]. The reduction in body water and intracellular water likely relates to exercise-induced glycogen depletion, adaptive changes in fluid-regulating hormones, and enhanced protein catabolism due to negative energy balance [20, 21]. It is worth noting that the unexpected decreases in muscle mass and basal metabolic rate may be related to uncontrolled protein intake in the study design, sustained negative energy balance, and a single training modality that lacked resistance training components [22, 23]. Future research studies combining FATmax training with resistance training may better preserve lean body mass while reducing fat, thereby further enhancing metabolic health benefits and reducing CVD risk.

In terms of liver function, the significant reduction in AST activity compared to pre-intervention (p 0.05) suggests improved liver health, which may indirectly reflect enhancements in cardiovascular risk factors [24]. However, no significant changes were observed in HDL-C or LDL-C levels. The lack of change may stem from insufficient exercise stimulus intensity at this specific intensity and modality, along with confounding factors such as the fatty acid composition of the diet, which was not strictly controlled [24, 25, 26, 27]. This limitation is particularly relevant in the context of Chinese university students, who often rely on canteen-prepared meals or takeout food, making it difficult to regulate oil and salt intake and thereby limiting the feasibility of personalized dietary management.

Regarding blood parameters, the observed reduction in red blood cell-related metrics may indicate exercise-induced physiological expansion of blood volume, release of erythropoietin (EPO), and enhanced antioxidant capacity, which are typically markers of good adaptation to regular exercise [28]. FATmax training stimulates the kidneys to release EPO through hypoxic stress; however, the activation of bone marrow hematopoiesis may take two or four weeks. Obese college students may experience more pronounced tissue hypoxia during training due to relatively poor cardiopulmonary function, resulting in a higher peak EPO release. Nevertheless, the rate of erythropoiesis still lags behind the rate of plasma volume expansion, leading to a short-term decrease in RBC, HGB, and HCT. This plasma volume expansion reduces blood viscosity, which can alleviate the low oxygen transport efficiency caused by dyslipidemia and blood hyperviscosity in obese populations, thereby enhancing the fat reduction effect of FATmax training [29]. Meanwhile, a lower HCT can decrease cardiac pumping resistance and reduce cardiovascular pressure in obese individuals with comorbidities such as hypertension and fatty liver disease [30]. It should be noted that if HGB levels drop below 130 g/L in males or 120 g/L in females and persist for more than 4 weeks, symptoms such as decreased maximal oxygen uptake, impaired exercise endurance, and increased fatigue may occur. Additionally, serum ferritin levels below 30 µg/L (or 12 µg/L in specific subgroups) can lead to reduced exercise performance, even if the criteria for overt anemia are not met [31]. The lack of expected change in the NLR may be due to FATmax training being of low to moderate intensity, which is less likely to cause severe inflammation or stress responses [32]. Other factors such as intervention duration, diet, or psychological stress may also have an impact [33]. Future studies could investigate incorporating high-intensity interval training (HIIT) to assess its additional effects on inflammatory markers and CVD risk.

Overall, improvements in cardiorespiratory function were a prominent finding of this study. The significant increases in peak VO₂, AT, percentage of predicted peak VO₂, FEV1/FVC ratio, and MMEF (all p 0.05) clearly indicate enhanced cardiorespiratory fitness and respiratory efficiency. The significant reductions in resting HR and DBP (p 0.05) indicate improved cardiac autonomic regulation and a decreased risk of cardiovascular issues [34, 35]. At the same time, there was a slight increase in the anaerobic threshold heart rate and maximum heart rate, indicating an elevation in the participants’ heart rate reserve. This further demonstrates that FATmax exercise enhances cardiac work efficiency and improves cardiovascular health [36]. Long-term regular endurance exercise can enhance respiratory muscle endurance through mechanisms like muscle fiber type transformation and increased mitochondrial content; however, improving respiratory muscle strength requires specialized respiratory muscle training. Obese college students typically have a relatively higher baseline respiratory load, and the proportion of oxygen consumption by respiratory muscles during exercise may be higher. If only FATmax training is performed without targeted respiratory muscle training, there may be little improvement in respiratory muscle strength. This could result in insufficient reduction of dead space ventilation or inadequate improvement in the tidal volume/respiratory rate ratio, ultimately having a limited impact on the VE/VCO₂ slope [37]. Furthermore, anxiety can stimulate sympathetic nerve excitation, increasing respiratory rate, decreasing tidal volume, and elevating dead space ventilation, which theoretically raises the VE/VCO₂ slope. If anxiety levels are not controlled or measured in a study, their influence on VE/VCO₂ may be confounded by “test-day status” [38]. Additionally, cardiopulmonary exercise testing (CPET) requires a stable rhythm and respiratory depth. If participants do not maintain regular breathing as instructed and experience respiratory rhythm fluctuations, the variability of VE/VCO₂ data will increase, obscuring the true training effect [39]. The unchanged MVV indicates that the training mode may not provide sufficient stimulation for respiratory muscle strength, suggesting that future studies could incorporate respiratory muscle training [40].

A significant decrease in ET-1 indicates that training may have improved vascular endothelial function, reduced vascular contractility, helped lower blood pressure, and alleviated strain on vascular walls, thereby exerting a protective effect on the cardiovascular system [41]. An increase in eNOS enhances vascular diastolic function, reduces peripheral vascular resistance, and promotes blood circulation, which exerts a positive impact on cardiovascular health. An increase in VEGF may help enhance myocardial blood and oxygen supply, promote the repair and regeneration of damaged blood vessels, and mitigate the development and progression of CVDs. Furthermore, VEGF may also play a role in regulating lipid metabolism and energy balance, thereby exerting a further beneficial effect on cardiovascular health [42, 43]. The improvements in these three indicators suggest that FATmax training can reduce the risk of cardiovascular diseases in obese college students through multiple pathways, such as improving vascular endothelial function, regulating vascular vasomotor status, and promoting angiogenesis.

Research has shown that CXCR1 and CXCR2 are closely involved in mediating inflammatory infiltration in cardiovascular diseases by participating in the recruitment and activation of leukocytes. In conditions such as atherosclerosis, CXCR1/2 inhibitors have demonstrated benefits in animal models, including reduced plaque area, improved lipid profiles, relief from ischemia-reperfusion injury, regulation of blood pressure, and limiting cardiac remodeling [44, 45]. GM-CSF can stimulate the proliferation, differentiation, and activation of granulocytes and macrophages, promote the generation of inflammatory cells, and exacerbate inflammatory responses in cardiovascular diseases. The serum GM-CSF level in patients with acute myocardial infarction is significantly correlated with the severity of the disease [46, 47]. IFN-$\gamma$ regulates the proliferation and migration of vascular smooth muscle cells, influencing vascular remodeling and impairing vascular endothelial function by promoting the expression of inflammatory factors [48, 49]. As a cytokine related to inflammation and immune regulation, IL-33 is associated with obesity-related chronic inflammation. An imbalance of the IL-33/suppression of tumorigenicity 2 (ST2) signaling pathway exacerbates inflammation and leads to myocardial damage [50, 51]. FATmax training induces vascular shear stress, activating eNOS, which promotes the synthesis and release of endothelial nitric oxide (eNO). eNO plays a dual role: it reduces the activity of CXCR1 and CXCR2 on the neutrophils and inhibits the expression of vascular endothelial adhesion molecules, thereby diminishing neutrophil chemotaxis and inflammatory infiltration. Additionally, eNO inhibits the activation of the Nuclear factor kappa-light-chain-enhancer of activated B cells (IFN-$\kappa$B) pathway, decreasing the synthesis and release of GM-CSF and IFN-$\gamma$ by macrophages, endothelial cells, T cells, and other cell types. Meanwhile, eNO promotes the degradation of IL-33 protein by regulating proteasome activity and indirectly inhibits IL-33 production through decreasing IFN-$\gamma$ levels, ultimately achieving a multi-target anti-inflammatory effect [52]. FATmax training can effectively reduce fat accumulation. In the obese state, adipose tissue releases numerous pro-inflammatory factors, and the secretion of these factors declines as adipose tissue is reduced [53]. During exercise, muscles secrete various myokines that exert immunomodulatory effects. These myokines can promote the expansion of regulatory T (Treg) cells, thereby inhibiting the production of IFN-$\gamma$ and alleviating inflammatory responses [54]. After 12 weeks of FATmax exercise intervention, the serum levels of CXCR1, CXCR2, GM-CSF, IFN-$\gamma$, and IL-33 in obese college students decreased significantly, which suggests that exercise may reduce the risk of cardiovascular diseases by inhibiting the chemotaxis, generation, and activation of inflammatory cells, as well as improving vascular endothelial function and the cardiovascular microenvironment.

However, none of the college students participating in the training adopted the recommended intervention of “incorporating resistance training after four weeks of training”. The main reasons included loss of training confidence, lack of suitable training facilities, and scheduling conflicts. In addition, participants did not adhere to the study’s control requirements. To address these challenges, future studies will refine the experimental design to minimize these limitations and develop more comprehensive intervention strategies to further strengthen the training program.

A 12-week FATmax exercise training program can significantly improve college students’ body composition, cardiovascular function, pulmonary function, and oxidative stress markers. It may serve as an effective intervention strategy to reduce the risk of CVD in the college student population. Moreover, combining FATmax training with resistance training and supplementing it with proper dietary management can improve body composition and relevant functional indicators, further reducing CVD risk factors.

The data that support the findings of this study are available from the corresponding author upon reasonable request.

ZWP designed the study; JY and FYS carried out experiments; ZWP, JY, and HMZ analyzed the data; HMZ, ZWP, JY, and FYS drafted and wrote the manuscript; HMZ, ZWP, JY, and FYS revised the manuscript. All authors contributed to the critical revision of the manuscript for important intellectual content. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Central Hospital of Dalian University of Technology (Date 21/10/2024/No. YN2024-134-32). Informed consent was obtained from all individual participants included in the study.

Not applicable.

This study was supported by the Central Hospital of Dalian University of Technology ‘Climbing Plan’ [grant number: 2024ZZ022].

The authors declare no conflict of interest.