INTRODUCTION
Obesity and metabolic disorders are pervasive problems affecting health worldwide. Midlife adults, especially women, experience unique health challenges due to hormonal and physiological changes that can contribute to an increased susceptibility to cardiovascular and metabolic diseases [
1,
2]. Aerobic exercise is widely recognized as an effective non-pharmacological strategy to improve metabolic health by modulating blood lipid profiles, glucose levels, and insulin sensitivity, and has received considerable attention owing to its potential to effectively control these risk factors across diverse populations [
3,
4].
Research has shown that aerobic exercise is known to improve lipid profiles, a critical factor in maintaining cardiovascular health. Kelly et al. [
5] demonstrated that moderate-intensity aerobic exercise (MIAE) has been shown to lower total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and triglycerides (TG) while enhancing high-density lipoprotein-cholesterol (HDL-C), which are important markers of improved cardiovascular health. Buzdagli et al. [
6] reinforced these findings by demonstrating that regular MIAE lead to improvements in blood lipid levels, supporting cardiovascular risk reduction. Further insight into the intensity-dependent effects of exercise on lipid metabolism revealed that high-intensity aerobic exercise (HIAE) has greater benefits for lipid regulation, potentially enhancing protection against cardiovascular diseases [
4,
7,
8].
Despite the well-documented benefits of exercise, gaps remain in our understanding of the optimal exercise intensity for maximizing metabolic benefits. Previous studies suggested that HIAE may provide greater benefits for lipid regulation, leading to enhanced cardiovascular protection [
4,
7,
8]. However, with few high-quality clinical trials systematically comparing the effects of different aerobic exercise intensities, the question of the ideal exercise intensity for target lipid outcomes persist. Additional studies are required to better understand how exercise intensity influences lipid metabolism and cardiovascular health, especially among high-risk groups like obese middle-aged women, who may experience different effects de-pending on the amount and intensity of exercise.
In addition to improving metabolism, aerobic exercise may benefit cognitive health by affecting levels of β-amyloid (Aβ), a biomarker associated with neurodegenerative diseases. Vasconcelos-Filho et al. [
9] demonstrated that exercise can reduce Aβ production in animal models of Alzheimer’s disease (AD), and a meta-analysis by Rodriguez-Ayllon et al. [
10] found that blood Aβ is reduced in people who engage in regular physical activity, regardless of their cognitive health status. However, Pucci et al. [
11] suggested that exercise interventions may not have a direct effect on Aβ-related pathology in dementia patients, and that the observed effects may stem from other mechanistic pathways. These findings call for further research to investigate the potential cognitive benefits of intensity-specific exercise, particularly in populations at risk of metabolic and neurodegenerative diseases.
In addition to lipid and Aβ modulation, aerobic exercise has demonstrated benefits for insulin resistance, a key factor in the development of type 2 diabetes and metabolic syndrome. Acute and regular aerobic exercise interventions demonstrated improvements in insulin sensitivity and reductions glucose levels, thereby promoting glycemic control and metabolic stability [
12,
13]. These findings emphasize that aerobic exercise is a useful intervention for managing metabolic risk factors. However, questions remain regarding how intensity-specific exercise affects these outcomes in the obese middle-aged population.
To address the limitations of previous studies, this research aims to explore the intensity-dependent effects of HIAE and MIAE on Aβ levels, metabolic markers, including insulin resistance and lipid profiles, among obese middle-aged females. Although previous studies have documented the benefits of aerobic exercise on metabolic and cognitive markers, few studies have systematically compared the specific mechanisms by which exercise intensity influences these outcomes. By investigating the shared and distinct pathways linking Aβ metabolism, metabolic health, and lipid regulation, this study seeks to provide a clearer understanding of how exercise intensity contributes to these markers. These findings will not only clarify the role of aerobic exercise intensity but also inform personalized exercise prescriptions for high-risk populations, addressing critical gaps in the existing literature.
METHODS
Participants
Participants were middle-aged women in their 50s residing in City G who fully comprehended the study’s purpose and agreed to participate of their own accord. They were classified as obese, with a body mass index (BMI) of 25 kg/m² or more and a body fat percentage of 30% or higher. They had not engaged in regular, structured exercise for at least 6 months and free of medical conditions, including cardiovascular or musculoskeletal diseases.
All participants underwent interviews and medical history reviews before the experiment to ensure their suitability for the study. During the experimental period, participants were instructed to refrain from behaviors that could influence the outcomes, such as alcohol consumption, smoking, medication use, or engaging in additional exercise outside the prescribed exercise program. All the participants were fully informed of the study procedures, potential risks, and experimental protocols. They were also provided with a consent document that clarified their right to withdraw from the study at any point without any obligation or penalty.
All participants were randomized to the HIAE (n=10), MIAE (n=10), and control (CON) (n=10) groups, and their physical characteristics are presented in
Table 1.
Procedures and Methods
The experiments in this study were conducted in the Exercise Physiology Laboratory of OO University, and before the experiment, all participants were fully informed about the procedures related to the experiment and possible risk factors during the experiment.
The procedure of this study consisted of a basic examination (body composition and exercise load test) and blood tests. The time and method related to the experiment were the same to minimize the margin of error of the experimental results. Participants were instructed to avoid engaging in strenuous physical activity on the day preceding the experiment, and each pre- and post-intervention participants was provided with adequate sleep.
Measuring body composition
The heights of all participants were measured using an automated body instrument (Fanics, FE810, Korea), and measurements of body weight (kg), fat percentage (%), and lean mass (kg) were conducted using equipment (InBody 720, Biospace, Korea) measured by bioelectrical resistivity. To ensure accuracy, participants refrained from eating for at least 8 hours and emptied their bowels and bladder just prior to measurement.
Measuring exercise testing
After resting for at least 10 min after the anthropometric measurements, a wireless heart rate monitor (FT2, Polar, Finland) was worn, and measurements were started after the heart rate reached the resting level. Each participant was measured on a treadmill (TM65 Treadmill, Quinton, USA) using a breath gas analyzer Metabolic Measurement System (TrueOne 2400, ParvoMedics, USA), and VO2max was measured using the Modified Bruce Treadmill Max Protocol, given that the participants were middle-aged women with no previous experience in professional fitness measurement.
Setting workout intensity
In this study, aerobic exercise intensity was set at 80-85% for the HIAE groups and 60-65% for the MIAE groups, based on the pre-collected VO2max of each participant, referring to the cardiorespiratory endurance exercise intensity ranges suggested by the ACSM (2021). We set the workouts to burn approximately 1,000 calories per week (350 calories per session), which is the recommended exercise goal for good health.
To set the exercise speed and duration, the target VO2 was calculated based on the pre-collected maximal oxygen uptake, which was then used to calculate the exercise speed and duration for each individual using a formula according to the ACSM (2021) (
Tables 2,
3, and
4).
Blood collection and analysis
Blood was collected twice, before and after aerobic exercise for 8 weeks, depending on the intensity of the exercise. All participants refrained from eating for a minimum of 8 h before blood collection, and hygiene was checked during blood collection to minimize infection. Around 5 mL of blood was collected from the antecubital vein using a vacutainer tube and a 22-gauge needle anticoagulated by a clinical pathologist when the resting heart rate (80 bpm) was reached by wearing a wireless heart rate monitor. Blood collection was performed at the same time and method as before and after exercise.
Blood samples were stored at room temperature for at least 30 min before being centrifuged at 3,000 rpm for 10- 15 min, plasma and serum were separated, transferred to 1.5 mL micro tubes, and stored at -70°C until the next analysis.
The β-amyloid assay was analyzed by Enzyme-Linked Immunosorbent assay (ELISA) method using Molecular device (USA), Human Amyloid beta Assay Kit (IBL, Japan) and Microplate Reader (Molecular device, USA).
Glucose was analyzed by the U.V. method at 340 nm using a biochemical analyzer (Hitachi, Japan, Hitachi 747), while insulin and HOMA-IR were analyzed by ELISA using a Human ELISA Kit with a Microplate Reader (Versa Max, Molecular device, USA). The HOMA-IR was derived using fasting insulin and glucose levels by substituting the following equation: HOMA-IR= [FPI (μU/mL) × FPG (mg/dL)]/405 (FPI: Fasting Plasma Insulin, FPG: Fasting Plasma Glucose).
TC, TG, LDL-C, and HDL-C levels were analyzed using automated modular analytics (c702; Roche, Germany) and the enzymatic colorimetric assay method.
Statistical analysis
All experimental results were calculated as mean (M) and standard deviation (SD) using the SPSS/PC+ Ver 26.0 K statistical program. Changes in body composition and blood parameters were analyzed using two-way repeated measures ANOVA for each group. When interactions were observed, post hoc analyses were conducted using paired and independent t-tests to examine the main effects of the independent variables. We defined statistical significance as p < 0.05 for all analyses.
DISCUSSION
This study examined the effects of 8 weeks of HIAE and MIAE on body composition, Aβ levels, metabolic markers (glucose, insulin, and HOMA-IR), and blood lipids (TC, TG, LDL-C, and HDL-C) in obese middle-aged women. Compared with the CON group, both HIAE and MIAE significantly improved body composition, Aβ levels, metabolic markers, and blood lipid profiles over time.
Both HIAE and MIAE groups exhibited significant reductions in body weight, body fat percentage, and BMI. These reductions were more pronounced in the exercise group than in the control group, supporting the efficacy of aerobic exercise in improving the body composition in obese individuals. This is consistent with the existing evidence for aerobic exercise and improved body composition. Our findings are supported by studies showing that high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) effectively reduced body fat and improved body composition in overweight and obese individuals. Keating et al. [
14] reported that both HIIT and MICT are effective for fat loss; however, HIIT may provide additional benefits in metabolic adaptations, with higher post-exercise oxygen consumption and improved fat oxidation rates, potentially leading to greater energy expenditure and sustained weight loss.
Mechanistically, aerobic exercise contributes to fat loss by stimulating hormonal changes and increasing lipolysis. Studies have shown that aerobic exercise lowers insulin levels and improves insulin sensitivity, which helps mobilize and use fat as fuel [
15]. In addition, fat loss observed in both HIAE and MIAE may reduce inflammation, as adipose tissue is known to contribute to systemic inflammation and insulin resistance, which are major risk factors for metabolic diseases [
16]. Therefore, reducing body fat through regular aerobic exercise may not only lower metabolic risk but also benefit overall health by reducing obesity-related inflammatory responses.
Both the HIAE and MIAE groups exhibited notable reductions in glucose, insulin, and HOMA-IR levels relative to the control group, indicating that aerobic exercise, regardless of intensity, improved insulin sensitivity and glycemic control. This observation aligns with prior studies showing that aerobic exercise improves glucose metabolism and reduces insulin resistance in populations at risk of metabolic syndrome. Hawley and Lessard [
17] observed that aerobic exercise enhances insulin sensitivity by increasing glucose uptake and promoting changes in skeletal muscle metabolism, which is the primary tissue for glucose disposal. Bird and Hawley [
18], also emphasized that the improvements in glucose and insulin levels from exercise are due to improved mitochondrial function and increased capillaries in the muscle tissue, which makes glucose transport and utilization more efficient. In particular, MIAE to HIAE has been shown to increase the expression of GLUT-4 transporters, which are important for insulin-mediated glucose uptake in muscle cells [
19]. This enhanced GLUT-4 expression contributes to improved insulin sensitivity and glycemic control. Enhanced mitochondrial biogenesis to support energy expenditure and upregulation of enzymes involved in glucose and fat oxidation are additional mechanistic insights that explain why insulin sensitivity is enhanced after exercise [
20]. This adaptation can be further enhanced by HIAE. HIAE often produces greater metabolic demands and thus promotes more substantial changes in mitochondrial and capillary density than moderate exercise, further improving metabolic flexibility and insulin sensitivity [
21].
These improvements in glycemic control and insulin sensitivity hold significant clinical relevance. Given that insulin resistance is a key component of metabolic syndrome and a precursor to type 2 diabetes, regular aerobic exercise may serve as a key non-drug intervention to prevent or delay the development of these conditions in high-risk populations such as obese middle-aged women. Colberg et al. [
22] recommend regular aerobic exercise to maintain insulin sensitivity and glycemic control in individuals with type 2 diabetes. Furthermore, metabolic risk factors like impaired insulin action often co-occur with cardiovascular disease risk factors, and improving these metabolic markers through aerobic exercise may provide further benefits for cardiovascular disease [
23].
Significant reductions in Aβ levels were observed in both the HIAE and MIAE groups, with a time-by-intensity interaction effect. These findings suggest that aerobic exercise, regardless of intensity, may contribute to lowering Aβ, a biomarker associated with cognitive decline in obese middle-aged women.
Aerobic exercise has been extensively studied for its potential to modulate levels of Aβ, a biomarker associated with cognitive decline and neurodegenerative diseases such as AD. Our findings are consistent with the existing literature that regular aerobic exercise can influence Aβ metabolism. A randomized controlled trial by Liu-Ambrose et al. [
24] demonstrated that physical activity, particularly aerobic exercise, is associated with reduced Aβ levels and improved cognitive performance in people with mild cognitive impairment. Similarly, Vasconcelos-Filho et al. [
9] reported that an aerobic exercise program reduced Aβ production and accumulation in an animal model and reviewed the various mechanisms by which exercise may reduce Aβ levels, including altered processing and formation of Aβ, increased non-amyloidogenic pathways, decreased amyloidogenic pathways, and increased Aβ degradation by neprilysin and insulin degrading enzyme. These studies reinforce the emerging view that regular aerobic activity has a protective effect on cognitive health, perhaps through mechanisms that affect Aβ metabolism and clearance.
The mechanism by which aerobic exercise can lower Aβ levels is particularly interesting. Physical activity is thought to increase blood flow and cerebrovascular function, potentially improving Aβ clearance from the brain [
25]. Moreover, the shared pathways between Aβ reduction and metabolic health may involve improved insulin signaling and reduced systemic inflammation, both of which are enhanced by aerobic exercise [
26,
27]. These mechanisms suggest that exercise-induced metabolic improvements, such as increased lipid metabolism and reduced insulin resistance, could indirectly influence Aβ clearance. Aerobic exercise is also has been shown to enhance the production of neurotrophic factors, including brain-derived neurotrophic factor, which support neuronal health and may influence Aβ clearance pathways [
28]. Additionally, aerobic exercise enhances neprilysin activity, an Aβ-degrading enzyme, which could further reduce Aβ accumulation [
29]. Improved lipid profiles, particularly elevated HDL-C levels observed in HIAE, may also facilitate Aβ clearance, as higher HDL-C has been associated with better cognitive function and reduced Aβ deposits [
30].
However, the effectiveness of aerobic exercise for preventing cognitive decline remains unclear in human studies. Vidoni et al. [
31] investigated the impact of a 52-week aerobic exercise regimen on amyloid deposition in cognitively healthy older individuals with increased brain amyloid levels. While aerobic training markedly enhanced cardiorespiratory capacity, it did not reduce amyloid deposition compared with the control group. Discrepancies between human and animal studies may be caused by differences in study design, duration and intensity of exercise intervention, and stage of disease progression among participants. Our study contributes to this evidence by demonstrating that HIAE and MIAE are associated with reduced Aβ levels in obese middle-aged women. These findings suggest that regular aerobic exercise, regardless of intensity, may serve as a non-pharmacologic strategy to modulate Aβ levels and potentially mitigate cognitive decline. Given the association between high Aβ levels and AD and other types of dementia, implementing aerobic exercise as part of a comprehensive health program for middle-aged adults, especially those at risk for metabolic and cognitive impairment, may provide dual benefits for both metabolic and cognitive health. Future studies should aim to elucidate optimal exercise parameters such as intensity, duration, and frequency to maximize the neuroprotective effects of aerobic exercise on Aβ metabolism and cognitive function.
The exercise program led to notable enhancements across all lipid parameters (TC, TG, LDL-C, and HDL-C), with greater reductions in TC, TG, and LDL-C in the HIAE and MIAE groups than in the CON group. In addition, post hoc analysis showed a significant increase in HDL-C levels in the HIAE group compared to the CON group (p = 0.000) and a trend toward a greater but not significant increase compared to the MIAE group (p = 0.058). These findings suggest that HIAE may be more effective than MIAE in regulating lipid profiles.
Our observations align with prior research highlighting the lipid-modulating effects of aerobic exercise. Garber et al. [
32] highlighted the positive contribution of aerobic exercise to blood lipid profiles and argued that it is an effective strategy for promoting cardiovascular health. Durstine et al. [
33] demonstrated that regular aerobic exercise provides cardioprotective effects through reductions in TC, LDL-C, and TG levels, coupled with enhancements in HDL-C levels. In addition, Kelly, Kelly and Tran [
5] reported that lipid levels improved in a similar pattern in women, with HIAE generally having a greater benefit in improving lipid profiles than low-intensity aerobic exercise.
Physiological mechanisms contributing to these changes include increased lipoprotein lipase activity, which enhances triglyceride removal and the upregulation of lecithin-cholesterol acyltransferase, which may promote HDL maturation and function [
33]. In addition, HIAE can downregulate hepatic lipase activity, which can lower LDL-C levels, a crucial element in mitigating cardiovascular disease risk [
34,
35].
This study has several limitations, including a small sample size and an 8-week time frame, which may not capture long-term effects. The limited sample size (n = 30) restricts the broader applicability of our findings. Future studies with larger cohorts and longer durations are essential to evaluate the sustained effects of HIAE and MIAE on Aβ reduction and metabolic health. Longitudinal studies could also help clarify the persistence of the effects of exercise to provide personalized exercise guidance for continued health improvement.
Our study underscores the importance of tailoring exercise intensity in middle-aged women, particularly those at a higher risk of cardiovascular disease or insulin resistance. HIAE has demonstrated superior effects on lipid profiles, especially HDL-C levels, making it a valuable option for individuals with a greater metabolic risk, as supported by Giacona et al. [
30]. Conversely, MIAE has proven to be an effective and accessible option for improving general metabolic health in broader populations. These findings suggest that HIAE should be prioritized for individuals at higher risk and incorporated into national health guidelines, whereas MIAE offers a universally applicable recommendation for promoting metabolic and cardiovascular health across diverse populations.