Anti-obesity effects of lutein and physical exercise on high-fat diet-induced obese ratsAbstract
This study aimed to evaluate the anti-obesity effects of lutein and physical exercise on obesity induced by a high-fat diet in male Wistar rats. There were 50 rats randomly divided into two groups. The control group (10 rats) was fed a standard diet, and the obese group (40 rats) was fed a high-fat diet to induce obesity for 17 weeks. After 12 weeks, 40 rats that were already obese were randomly divided into 4 groups as follows: a high-fat diet (HFD), a high-fat diet plus lutein (HFD + L), a high-fat diet plus physical exercise (HFD + Ph), and a high-fat diet plus lutein plus physical exercise (HFD + L + Ph) for 5 weeks. At the end of the experiment, the fasting blood glucose levels, lipid profile, and leptin levels in serum were measured. Also, the histopathological changes in the heart tissue were assessed. The L and Ph reduce body weight and significantly decrease abdominal fat accumulation in the HFD-fed rats. Moreover, the L and Ph significantly decreased fasting blood glucose and leptin levels, improved the lipid profile efficiently, and restored the normal histological structure of the heart. This study proved that L and Ph may be potential strategies to manage obesity by effectively alleviating the metabolic changes caused by HFD. Furthermore, L and Ph together affected biochemical parameters better than either intervention alone.
Keywords:
obesity; high-fat diet; lutein; physical exercise; lipid profile
Resumo
Este estudo teve como objetivo avaliar os efeitos antiobesidade da luteína e do exercício físico na obesidade induzida por dieta rica em gordura em ratos Wistar machos. Foram utilizados 50 ratos, divididos aleatoriamente em dois grupos. O grupo controle (10 ratos) recebeu uma dieta-padrão, enquanto o grupo obeso (40 ratos) recebeu uma dieta rica em gordura para indução da obesidade durante 17 semanas. Após 12 semanas, os 40 ratos que apresentavam obesidade foram divididos aleatoriamente em 4 grupos, conforme segue: dieta rica em gordura (HFD), dieta rica em gordura mais luteína (HFD + L), dieta rica em gordura mais exercício físico (HFD + Ph) e dieta rica em gordura mais luteína e exercício físico (HFD + L + Ph), durante 5 semanas. Ao final do experimento, foram medidos os níveis de glicemia de jejum, o perfil lipídico e os níveis séricos de leptina. Além disso, foram avaliadas as alterações histopatológicas no tecido cardíaco. A luteína (L) e o exercício físico (Ph) reduziram o peso corporal e diminuíram significativamente o acúmulo de gordura abdominal nos ratos alimentados com HFD. Além disso, a L e o Ph reduziram significativamente a glicemia de jejum e os níveis de leptina, melhoraram o perfil lipídico de forma eficiente e restauraram a estrutura histológica normal do coração. Este estudo demonstrou que a L e o Ph podem ser estratégias potenciais para o controle da obesidade, atenuando de modo efetivo as alterações metabólicas causadas pela HFD. Além disso, a combinação de L e Ph influenciou os parâmetros bioquímicos de maneira mais eficaz do que qualquer uma das intervenções isoladas.
Palavras-chave:
obesidade; dieta rica em gordura; luteína; exercício físico; perfil lipídico
1. Introduction
Globally, obesity has emerged as a serious health issue that affects individuals of all ages and genders. Since 1980, the number of people who are obese has doubled, and now up to 39% of the world’s population is obese. By 2030, obesity will affect nearly 58% of the population. This significant increase in obesity prevalence results from a change in diet, decreased physical activity, and socioeconomic factors (Blüher, 2019). The major cause of obesity is an imbalance between calories ingested and calories burned (Boutari and Mantzoros, 2022). Obesity has been associated with numerous disturbances such as hypertension, cardiovascular diseases, type 2 diabetes mellitus, dyslipidemia, and certain types of cancer (Bollapragada et al., 2017; Fock and Khoo, 2013).
Because a high-fat diet (HFD) can replicate the effects of obesity in humans, it is frequently used to induce obesity in rat models (Abdul Kadir et al., 2015; Alatawi et al., 2023). When compared to regular diets, an HFD is defined by a larger percentage of calories coming from fat and a lower percentage from proteins and carbs. Several studies found that prolonged consumption of an HFD was associated with significant increases in body weight, abdominal fat accumulation, dyslipidemia, hyperglycemia, and hyperleptinemia (Abdul Kadir et al., 2015; Acikel Elmas et al., 2019; Al-Thepyani et al., 2022; Baz et al., 2022). Obesity is typically treated with drugs and/or surgery, both of which have significant health risks and a high likelihood of recurrence. As a result, recent studies have focused on employing natural products and physical activity as alternatives and effective methods for controlling obesity without any side effects (Alatawi et al., 2023; Ammar et al., 2017; Karri et al., 2019; Oharomari et al., 2021).
Carotenoids have grown in relevance in recent years as a result of their well-known health benefits (Alatawi et al., 2023; Salem, 2015). More than 1100 types of carotenoids have been identified in nature. Lutein is one of the most prevalent carotenoids commonly present in orange, yellow, and green fruits and vegetables such as carrots, cantaloupe, yellow peppers, corn, spinach, celery, kiwi, marigold, avocado, and broccoli (Alatawi et al., 2023; Nwachukwu et al., 2016; Ouyang et al., 2019). Lutein cannot be produced by humans; therefore, they must obtain it through dietary supplements (Carpentier et al., 2009). Numerous pharmacological properties of lutein include antioxidant, anti-inflammatory, and anti-adipogenic properties as well as neuroprotective, hepatoprotective, and cardioprotective activities (Alatawi et al., 2023; Morell and Fiszman, 2017; Nwachukwu et al., 2016; Sindhu et al., 2010).
The antioxidant effects of lutein are attributed to its unique structure, particularly the presence of conjugated double bonds and hydroxyl groups. The conjugated double bond acts as a powerful antioxidant by donating electrons and reacting with free radicals to form a more stable product (Ahn et al., 2021; Perrone et al., 2016). Lutein's anti-inflammatory effect is mediated through inhibiting the expression of genes involved in the generation of inflammatory cytokines, such as the nuclear factor kappa B (NF-κB) pathway (Kim et al., 2012; Li et al., 2018; Perrone et al., 2016). The anti-adipogenic effect of lutein is achieved by inhibiting lipogenesis, decreasing intracellular lipid and adipose weight, and improving dyslipidemia effectively (Liu et al., 2017; Seo et al., 2016).
Exercise is one of the most important components of the overall approach to treating obesity. When performed regularly and properly, exercise has a powerful protective effect against obesity comorbidities. Physical exercise not only contributes to an increased energy expenditure and fat loss but also reduces obesity-related cardiometabolic health risks (Alatawi et al., 2023; Murase et al., 2006; Petridou et al., 2019; Zalaqi et al., 2022). Physical exercise triggers a range of physiological responses that are cardioprotective, including cardiac growth, increased coronary blood flow, improved myocardial contractility, regeneration of cardiomyocytes, reduced likelihood of myocardial infarction, and increased cardiomyocyte formation (Gronek et al., 2020; Lavie et al., 2019; Lazar et al., 2013). Exercise also lowers circulating indicators of systemic inflammation by enhancing antioxidant enzyme activity (Acikel Elmas et al., 2019; Lavie et al., 2019). It has also been demonstrated to be beneficial for lowering blood pressure, improving lipid profiles, and reducing hyperglycaemia (Acikel Elmas et al., 2019; Al-Thepyani et al., 2022; Gheibi et al., 2017; X. Q. Yang et al., 2016)
Based on the established beneficial effects of lutein and physical exercise on overall health, and after reviewing existing literature, no studies have yet investigated the combined impact of lutein supplementation and physical exercise on obesity and associated metabolic disorders. Therefore, the present study aims to evaluate the anti-obesity effects of lutein in conjunction with physical exercise by assessing lipid profiles, fasting glucose levels, and leptin levels. Additionally, the study assesses histopathological alterations in the cardiac tissue of male Wistar rats fed an HFD.
2. Materials and Methods
2.1. Chemicals and kits
Lutein (98% purity), extracted from marigold flowers, was obtained from Xi'an Tongze Biotech Co., Ltd., Xi’an, China. The standard diet was obtained from the King Fahd Medical Research Center (KFMRC), King Abdulaziz University, Jeddah, Saudi Arabia. Casein was purchased from Xi’an Harmonious Natural Bio-Technology Co., Ltd., Xi’an, China. Avitone premix powder (vitamins and minerals mixture) was purchased from Star Laboratories, Lahore, Pakistan. Commercial cow butter and sunflower oil were purchased from a local market in Jeddah, Saudi Arabia. DL-methionine and a leptin enzyme-linked immunosorbent assay (ELISA) kit (Cat. No. SEKR-0051) were purchased from Solarbio Science and Technology Co., Ltd., Beijing, China (Alatawi et al., 2023).
2.2. Animals
Fifty male Wistar albino rats, each weighing 200 ± 20g and aged 7 weeks, were obtained from the Animal House Unit at KFMRC. They were housed in polypropylene cages under controlled conditions (temperature maintained at 23 ± 2°C, 65% relative humidity, and a standard 12-hour light/dark cycle) with ad libitum access to a standard diet and water. The rats were allowed to acclimate to these laboratory conditions for a week before the study. The Biomedical Ethics Research Committee at King Abdulaziz University approved the study protocol (Approval No. 548-20), which adhered to the Animal Care and Use Committee regulations at KFMRC (Alatawi et al., 2023).
2.3.Diets
In this study, two experimental diets were used: a standard diet and a high-fat diet (HFD). The standard diet contained 387 kcal/100 g and consisted of 67.7% carbohydrates, 20.0% protein, 4.0% fat, 3.5% fiber, 4.5% mixed vitamins and minerals, and 0.3% choline chloride. The HFD contained 529 kcal/100 g and consisted of 40.4% carbohydrates, 19.4% protein, 32.2% fat, 2.1% fiber, 5.6% mixed vitamins and minerals, 0.1% choline chloride, and 0.2% DL- methionine. The high-fat diet was prepared by mixing powdered standard diet (59.59%), butter (29.79%), casein (7.45%), DL-methionine (0.2%), and mixed vitamins and minerals (2.97%) [6,8,32]. The HFD was prepared weekly, stored at 4 °C, and allowed to reach room temperature before being provided to the rats.
2.4. Preparation of treatment
Lutein (50 mg/kg/day) was suspended in sunflower oil (2 ml/kg/day) to obtain a homogeneous suspension and stored in the dark at 4 °C until use. Before each administration, the suspension was warmed in a water bath at 30 °C for 20 min, vortex-mixed to ensure homogeneity, and then administered to the rats (Alatawi et al., 2023; Pierine et al., 2014). The selected lutein dose (50 mg/kg/day) was chosen according to previously published studies reporting its protective effects against obesity and its associated metabolic alterations (Narayanamurthy et al., 2018; Qiu et al., 2015; Sharavana et al., 2017).
2.5. Experimental design
After a one-week acclimatization period, the fifty rats were randomly divided into two groups: a control group (n = 10) and an obese group (n = 40). The control group was fed the standard diet, whereas the obese group was fed an HFD throughout the 17-week experimental period. After 12 weeks, the mean body weight was compared between the control and obese groups to confirm the induction of obesity [5,37]. Following obesity induction, the 40 obese rats were randomly assigned to four experimental groups (n = 10 per group): HFD, HFD + L, HFD + Ph, and HFD + L + Ph. Treatment was initiated at the beginning of week 13 and continued for five weeks. During this period, the control and HFD groups received sunflower oil (2 mL/kg/day) by oral gavage. The HFD + L group received lutein (50 mg/kg/day) by oral gavage. The HFD + Ph group received sunflower oil (2 mL/kg/day) by oral gavage and underwent swimming exercise, while the HFD + L + Ph group received lutein (50 mg/kg/day) by oral gavage and underwent swimming exercise (Alatawi et al., 2023) (Figure 1).
Experimental design. High-fat diet group (HFD), high-fat diet + lutein group (HFD + L), high-fat diet + physical exercise group (HFD + Ph), high-fat diet + lutein + physical exercise group (HFD + L + Ph), and n: number of rats.
2.6. Exercise protocol
The swimming exercise was performed in the plastic tank (dimensions: 78 cm length × 56 cm width × 48 cm depth) with water temperature of 32 ± 2 °C. Before the treatment period, the rats in exercise groups (HFD + Ph and HFD + L + Ph) were acclimated to the water for one week. During the acclimation period, the rats initially swam for 10 min/day, and the swimming duration was increased by 10 min/day until they were able to swim continuously for 60 min/day (Riahi and Riahi, 2016). In the next 5 weeks of treatment, the rats swam for 60 min/day in the morning from 9:00 to 10:00 am. To prevent hypothermia, rats were dried after each exercise session and placed in a warm environment (Alatawi et al., 2023; Riahi and Riahi, 2016). The swimming exercise protocol (60 min/day) was adapted from previously published studies reporting its effectiveness in improving obesity and related metabolic disorders (Acikel Elmas et al., 2019; Al-Thepyani et al., 2022; Murase et al., 2006; Zalaqi et al., 2022).
2.7. Body weight, food intake, and caloric intake measurements
Body weight was measured for each rat at the beginning of the experimental period and then recorded weekly throughout the study. Food intake was recorded daily by subtracting the amount of food remaining from the amount of food provided. Caloric intake was calculated using the following equation: caloric intake (kcal/day) = (food intake (g/day) × dietary energy (kcal/100 g) / 100) (Bhandari et al., 2010).
2.8. Collection of blood and tissue samples
By the end of the experimental period, overnight-fasted rats were anesthetized with isoflurane (5% for induction and 3% for maintenance), delivered in oxygen at a flow rate of 2 L/min using an induction chamber. Blood samples were collected from the retro-orbital sinus and centrifuged at 3000 rpm for 10 min. The separated serum was stored at -80°C until biochemical analysis. After blood collection, the rats were sacrificed by an overdose of isoflurane (Alatawi et al., 2023). The abdominal cavity was then opened, and the heart was removed, weighed, and fixed in 10% buffered formalin for 24 h for histological analysis. Each rat’s abdominal fat and heart were weighed to calculate their relative weights using the following formula: relative organ weight = (organ weight/final body weight) × 100 (C. Yang et al., 2018).
2.9. Biochemical analysis
The levels of fasting blood glucose and lipid profile [total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL)] in serum were analyzed at the Clinical Laboratory of King Fahd Armed Forces Hospital, Jeddah, Saudi Arabia, using a COBAS® 8000 modular analyzer. The leptin level in serum was measured by using an ELISA kit according to the manufacturer’s instructions.
2.10. Histological analysis
Following fixation, heart samples were dehydrated through graded concentrations of alcohol, cleared in xylene, embedded in paraffin wax, and sectioned into 5 µm thickness. The sections were stained with hematoxylin and eosin (H&E) (Acikel Elmas et al., 2019; Slaoui and Fiette, 2011). Sections from the caudal region of the left ventricular wall were examined under a light microscope and photographed at ×400 magnification.
2.11. Statistical analysis
Statistical analyses were performed using GraphPad Prism 9.0 (GraphPad Software Inc, USA). Data normality was assessed using the Shapiro–Wilk test. Body weight data were analyzed using two-way repeated measures analysis of variance (ANOVA), whereas all other data were analyzed using one-way ANOVA followed by a Tukey’s multiple comparisons test. Data are presented as the mean ± standard error of the mean (SEM). Differences were considered statistically significant at p < 0.05.
3. Results
3.1. Effect of lutein and physical exercise on body weight, relative weight of abdominal fat and heart, food intake, and caloric intake
The body weight results are presented in Table 1. At the beginning of the experiment (Week 0), no significant differences in body weight were observed among the experimental groups (p > 0.05). Before treatment (Week 12), rats in the HFD groups (HFD, HFD + L, HFD + Ph, and HFD + L + Ph) exhibited significantly higher body weight than the control group (p < 0.0001), confirming successful obesity induction. After treatment (week 17), body weight remained significantly higher in the HFD group and all treated groups (HFD + L, HFD + Ph, and HFD + L + Ph) than in the control group (p < 0.0001). However, rats treated with lutein and/or physical exercise did not significantly lower (p ˃ 0.05) body weight compared to the HFD group. Also, there was no significant difference (p ˃ 0.05) in body weight between all treated groups (HFD + L, HFD + Ph, and HFD + L + Ph). The body weight results have been published previously (Alatawi et al., 2023).
Body weight, relative weight of abdominal fat and heart, food intake, and caloric intake for different experimental groups.
Moreover, as shown in Table 1, there was a substantially higher (p < 0.0001) relative weight of abdominal fat in the HFD group compared to the control group. Conversely, rats treated with lutein and/or physical exercise (HFD + L, HFD + Ph, and HFD + L + Ph) showed markedly lower (p ˂ 0.01, p ˂ 0.01, and p ˂ 0.001, respectively) in the relative weights of abdominal fat compared to the HFD group. However, there was no significant difference (p ˃ 0.05) in the relative weight of abdominal fat between all treated groups (HFD + L, HFD + Ph, and HFD + L + Ph). However, there were no significant differences (p ˃ 0.05) in the relative heart weight among all groups (control, HFD, HFD + L, HFD + Ph, and HFD + L + Ph) (Table 1).
Also, as demonstrated in Table 1, the HFD group and all treated groups (HFD + L, HFD + Ph, and HFD + L + Ph) exhibited significantly lower food intake and higher caloric intake (p ˂ 0.0001) compared to the control group. However, there was no significant difference (p ˃ 0.05) in food intake and caloric intake observed between the HFD group and all treated groups (HFD + L, HFD + Ph, and HFD + L + Ph). Moreover, there was no significant difference (p ˃ 0.05) in food intake and caloric intake between all treated groups (HFD + L, HFD + Ph, and HFD + L + Ph).
3.2.Effect of lutein and physical exercise on fasting blood glucose levels
Fasting blood glucose (FBG) levels were significantly higher (p < 0.0001) in the HFD group when compared to the control group. Nonetheless, rats treated with lutein and/or physical exercise (HFD + L, HFD + Ph, and HFD + L + Ph) showed significantly lower (p ˂ 0.0001) FBG levels compared to the HFD group. Moreover, there was no significant change (p ˃ 0.05) in FBG levels between all treated groups (HFD + L, HFD + Ph, and HFD + L + Ph) and when compared to the control group (Figure 2A).
Effect of lutein and physical exercise on fasting blood glucose levels (A) and leptin levels (B) in different experimental groups. Data are presented as Mean ± SEM. HFD group, HFD + L group, HFD + Ph group, and HFD + L + Ph group after 17 weeks (10 rats/group). Significant *, **, ***, and **** at p < 0.05, p < 0.01, p < 0.001, and p < 0.0001 versus the control group and HFD groups. Significant #, ##, and ### at p < 0.05, p < 0.01, and p < 0.001, respectively, versus the HFD group and treated HFD groups, and ns = no significance.
3.3. Effect of lutein and physical exercise on leptin levels
Leptin levels were considerably higher (p < 0.0001, p < 0.001, p < 0.01, and p < 0.05, respectively) in the HFD group and all treated groups (HFD + L, HFD + Ph, and HFD + L + Ph) than in the control group. Conversely, rats treated with lutein and/or physical exercise (HFD + L, HFD + Ph, and HFD + L + Ph) revealed a drastically lower (p ˂ 0.01, p ˂ 0.05, and p ˂ 0.0001; respectively) leptin level compared to the HFD group. However, there was no significant change (p ˃ 0.05) in leptin levels between all treated groups (HFD + L, HFD + Ph, and HFD + L + Ph) (Figure 2B).
3.4. Effect of lutein and physical exercise on the lipid profile
Figures 3A-D represent the levels of the lipid profile, such as triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) of all groups. The HFD group had significantly higher (p ˂ 0.0001) TG, TC, and LDL levels and significantly lower (p ˂ 0.0001) HDL levels than the control group. However, rats in the HFD + L, HFD + Ph, and HFD + L + Ph groups had considerably higher (p < 0.001, p < 0.0001, and p < 0.05; respectively) TG and TC levels and no significant difference (p ˃ 0.05) in LDL and HDL levels compared to the control group. Nevertheless, rats treated with lutein and /or physical exercise (HFD + L, HFD + Ph, and HFD + L + Ph) led to a substantially lower (p ˂ 0.001, p ˂ 0.01, and p ˂ 0.0001; respectively) in LDL and TG levels and a considerable higher (p ˂ 0.001, p ˂ 0.01, and p ˂ 0.0001; respectively) in HDL levels compared to the HFD group. Moreover, TC levels were significantly lower (p ˂ 0.001 and p ˂ 0.0001, respectively) in HFD + L and HFD + L + Ph groups, and there was no significant difference in TC levels in the HFD + Ph group compared to the HFD group. In addition, there was no significant change (p ˃ 0.05) in TG, TC, LDL, and HDL levels between all treated groups (HFD + L, HFD + Ph, HFD + L + Ph).
Effect of lutein and physical exercise on triglyceride levels (A), total cholesterol levels (B), low-density lipoprotein levels (C), and high-density lipoprotein levels (D) in different experimental groups. Data are presented as Mean ± SEM. HFD group, HFD + L group, HFD + Ph group, and HFD + L + Ph group after 17 weeks (10 rats/group). Significant *, ***, and **** at p < 0.05, p < 0.001, and p < 0.0001 versus the control group and HFD groups. Significant #, ##, ###, and #### at p < 0.05, p < 0.01, p < 0.001, and p < 0.0001, respectively, versus the HFD group and treated HFD groups, and ns = no significance.
3.5. Histological results
The examination of the longitudinal and transverse sections of the left ventricular wall from the control group, as presented in Figures 4A and B, showed the normal architecture in the form of branching and anastomosing cardiac muscle fibers running in different directions with little interstitial space that contained some blood capillaries. These fibers showed poorly developed cross striation and acidophilic cytoplasm with elongated vesicular nuclei, usually centrally located. In the HFD group, as displayed in Figures 4C-F, there was an alteration in the form of the waviness, disarrangement, and fragmentation of some cardiac muscle fibers with wider spaces between them. Also, congested blood vessels and inflammatory cell infiltration were seen. In addition, some cardiac muscle fibers showed pyknotic nuclei while others showed hyaline degeneration. However, in the HFD + L group, as observed in Figures 5C and D, the examination showed mild changes when compared with the HFD group. However, some sections revealed minimal damage, such as the waviness of some muscle fibers and congested blood vessels. Also, in the HFD + Ph group, the examination of the longitudinal histopathological sections of the left ventricular wall Figures 5A and B showed regression of the histopathological changes and abnormalities as compared with the HFD group. Some changes were still observed, such as waviness of cardiac muscle fibers and widening of interstitial spaces, and congested blood vessels. In the HFD + L + Ph group, the examination of the longitudinal and transverse sections of the left ventricular wall, as shown in Figures 5E and F, showed a nearly normal histological structure similar to the control group, with the restoration of histopathological changes.
Photomicrographs of the left ventricular wall of control and HFD groups. Longitudinal and transverse sections of A and B from the control group show the normal structure in the form of branched and anastomosing cardiac muscle fibers (C), with acidophilic cytoplasm and poorly developed cross striation, and the presence of oval central nuclei (N). Notice the presence of narrow interstitial spaces between the fibers that contain some nuclei of fibroblasts ) and blood vessels (bv). Longitudinal sections C and D from the HFD group show wavy and disorganized cardiac muscle fibers (C). Notice the presence of wide interstitial spaces ) with dilated and congested vessels (bv) and inflammatory cell infiltration (ICI). Transverse sections E and F from the HFD group show wide interstitial spaces ) between cardiac muscle fibers (C) and congested blood vessels (bv). Some cardiac muscle fibers (C) contain pyknotic nuclei (thin arrow), while some other fibers show hyaline degeneration (thick arrow).
Photomicrographs of the left ventricular wall of HFD + Ph, HFD + L, and HFD + L + Ph groups. Longitudinal and transverse sections A and B from the HFD + Ph group show wavy cardiac muscle fibers (C), wide interstitial spaces ) with congested blood vessels (bv), and some fibers (C) with hyaline degeneration (thick arrow). Longitudinal and transverse sections C and D from the HFD + L group show the normal appearance of cardiac muscle fibers (C) with narrow interstitial spaces ) and blood vessels (bv). Notice the presence of small blood vessels between the muscle fibers (bv). Longitudinal and transverse sections E and F from the HFD + L + Ph group with nearly normal structure in the form of branched and anastomosing cardiac muscle fibers (C), narrow interstitial spaces ), and blood vessels (bv), and normally appearing nuclei (arrow).
4. Discussion
Obesity is a multifactorial metabolic disease characterized by excessive adiposity and associated with disturbances in glucose and lipid metabolism, adipokine signaling, and cardiovascular function. Lifestyle modification remains a central component of obesity management, particularly dietary intervention, increased physical activity, and behavioral support. Importantly, the health benefits of physical activity are not entirely dependent on weight loss, as exercise can improve several cardiometabolic outcomes even when changes in body weight are modest (Al-Thepyani et al., 2022; Stonehouse et al., 2016). Recently, natural products have been studied as an alternative to pharmaceutical medications, which cause undesirable side effects in treating and reducing obesity (Petridou et al., 2019). This study aimed to investigate the anti-obesity effects of lutein and physical exercise on obesity induced by a high-fat diet in male Wistar rats.
In this study, feeding rats a high-fat diet (HFD) led to significantly higher body weight and relative abdominal fat weight in the HFD group compared to the control group, and this result is consistent with a recent studies (Alatawi et al., 2023; Baz et al., 2022; Bhandari et al., 2010; Sahraoui et al., 2020). More recent evidence also confirms that HFD-induced obesity is accompanied by marked accumulation of abdominal and epididymal adipose tissue and metabolic disturbances (Gopal et al., 2023). After treatment with lutein and/or physical exercise, body weight appeared to be a trend lower, but it was not statistically significant, as well as abdominal fat weight was reduced significantly in all treated groups (HFD + L, HFD + Ph, and HFD + L + Ph) compared to the HFD group. Rats in the HFD + L + Ph group had slightly lower body weight and abdominal fat weight. The results of the current study suggest that L and Ph combined can reduce HFD-induced obesity by preventing higher body weight and abdominal fat. Recent research by (Qiu et al., 2015)on rats treated with lutein revealed that no significant difference was observed in body weight, but abdominal fat weight was significantly lower compared with rats fed HFD. In addition, according to (Wang et al., 2021), lutein administration may be a potential strategy for preventing excessive lipid accumulation and obesity because it reduces body weight and abdominal fat index ratio. Moreover, physical exercise groups (HFD + Ph and HFD + L+ Ph) showed the least body weight, indicating that physical exercise may help halt or slow the development of obesity. This finding is consistent with earlier studies showing that regular exercise can enhance energy metabolism in the body, aiding in weight control and lowering obesity rates (Alatawi et al., 2023; Jakicic and Otto, 2006; Kang et al., 2019; X. Q. Yang et al., 2016). A recent network meta-analysis of 84 randomized controlled trials similarly demonstrated that exercise can reduce visceral adipose tissue in individuals with overweight or obesity (Chen et al., 2024). A study by (Petridou et al., 2019)reported that even without weight loss, regular exercise can improve the metabolic consequences of obesity.
In addition, this study found that the HFD groups (HFD, HFD + L, HFD + Ph, and HFD + L + Ph) exhibited lower food intake and higher caloric intake than the control group. HFD-fed rats consumed less food by weight but had a higher caloric intake than control rats, reflecting the greater energy density of the HFD (Baz et al., 2022; Kostrycki et al., 2019; Riahi and Riahi, 2016). However, the least food intake and caloric intake were seen in the physical exercise groups (HFD + Ph and HFD + L + Ph). This finding emphasizes that food mass and energy intake should be considered separately when evaluating feeding behavior in HFD models. The lower food intake observed in the exercise groups may indicate an effect of physical activity on feeding behavior or energy regulation. However, exercise does not uniformly suppress appetite or energy intake. Systematic reviews indicate that the response varies according to exercise modality, duration, intensity, and metabolic status (Almesbehi et al., 2023; Grigg et al., 2023). Similarly, other research has shown that rats that are fed a high-fat diet and do physical exercise usually eat less and burn fewer calories(Levin and Dunn-Meynell, 2006; Rocha et al., 2016). Since exercise is a stress agent, it is possible that it suppresses hunger and regulates energy balance by influencing the release of anorectic hormones and/or increasing the sensitivity of their receptors (Blundell et al., 2015; Schubert et al., 2013). Moreover, other research has indicated that exercise decreases hunger and enhances energy expenditure (Baek et al., 2020; El Elj et al., 2011; Hillman et al., 2024). Rats receiving both lutein and physical exercise showed numerically lower body weight and abdominal fat weight. However, because the differences between the individual interventions and the combined treatment were not statistically significant, these findings could not be interpreted as evidence of a synergistic effect. Rather, they indicate that combining lutein with exercise was compatible with attenuation of HFD-induced adiposity. Whether lutein enhances the anti-obesity effects of exercise would require a study specifically designed to test an interaction between the two interventions.
HFD feeding also produced a significant increase in fasting blood glucose, consistent with the impaired glucose homeostasis commonly associated with diet-induced obesity (Lasker et al., 2019; Zalaqi et al., 2022). Nonetheless, fasting blood glucose levels in the HFD + L, HFD + Ph, and HFD + L + Ph groups were significantly lower due to the administration of lutein and/or exercise performance. This result is consonant with (Qiu et al., 2015; Sharavana et al., 2017), found that lutein lowered FBG levels in obese animals, as well as more recent evidence showing that lutein attenuates HFD-induced glucose intolerance (Gopal et al., 2023). These findings suggest that the metabolic effects of lutein extend beyond adipose tissue accumulation. Moreover, there is evidence that regular exercise can enhance glucose tolerance, insulin secretion, and pancreatic ß-cell activity (Corrêa et al., 2015; Nakhaei et al., 2019). Previous research has demonstrated that glucose uptake efficiency is enhanced through physical activity, with a positive correlation observed between glucose absorption and both exercise load and intensity. Furthermore, that glucose uptake efficiency improves with exercise with a positive correlation between glucose absorption and both physical load and exercise intensity. The increased glucose absorption is mediated by the stimulation of insulin secretion and the regulation of cellular response to insulin (Farman and Ghaffar, 2020; Roy and Parker, 2007). Exercise may improve glucose regulation through mechanisms that differ partly from those of lutein. Skeletal muscle is a major site of glucose disposal, and muscle contraction stimulates glucose uptake through pathways that can operate independently of insulin. Exercise also increases insulin sensitivity, facilitating glucose clearance after exercise. Current mechanistic evidence identifies translocation of glucose transporter 4 (GLUT4) to the muscle cell membrane as a central component of both insulin- and contraction-stimulated glucose uptake (Richter et al., 2025). Therefore, the lower fasting glucose in the exercise groups may reflect improved peripheral glucose handling rather than simply increased insulin secretion. This interpretation is more consistent with current understanding of exercise physiology than attributing the response primarily to stimulation of pancreatic insulin release.
Obesity is characterized by alterations in circulating adipokine concentrations due to the excessive fat accumulation and dysfunction of adipose tissue (Forny-Germano et al., 2019). Leptin is secreted predominantly by adipocytes and normally contributes to the regulation of appetite and energy balance. Circulating leptin concentrations generally increase with adipose tissue mass, and persistent hyperleptinemia in obesity is commonly associated with reduced responsiveness to leptin signaling (Al-Thepyani et al., 2022; Israel et al., 2021). In the present study, serum leptin was significantly elevated in HFD-fed rats compared with controls, consistent with the increased abdominal adiposity observed in this group and with previous HFD studies (Baz et al., 2022; Kilany et al., 2020). Conversely, after treatment with lutein and/or physical exercise, leptin levels were significantly lower in HFD + L, HFD + Ph, and HFD + L + Ph groups compared with the HFD group. This result is consonant with recent studies showing that carotenoids can reduce leptin levels due to their anti-adipogenic, antioxidant, and anti-inflammatory effects (Al-Thepyani et al., 2022; Riaz et al., 2021). Moreover, studies on obese animals revealed that leptin levels were considerably lower after exercise (Al-Thepyani et al., 2022; Kolieb et al., 2022). The reduction in leptin in the exercise-treated animals is also consistent with more recent evidence. A 2023 systematic review and meta-analysis reported that exercise interventions can alter circulating adipokines in individuals with overweight or obesity, although the magnitude of the response depends on factors including body composition and intervention duration (Khalafi et al., 2023). Another meta-analysis found that dietary intervention and combined diet-exercise interventions reduce circulating leptin, while the independent effect of exercise is more variable (Zhou et al., 2025). However, there are two possible explanations for exercise's effect on leptin levels. The first is that exercise helps by reducing the dysregulated expression of adipokines produced by adipose tissue, which may help attenuate the inflammation induced by obesity (Sakurai et al., 2013). Second, the proinflammatory effects of adipokines may be neutralized or at least mitigated by myokines, which are produced and released into the bloodstream when muscles contract and relax during exercise (Pedersen and Febbraio, 2012; Sakurai et al., 2013). Rats receiving both lutein and physical exercise showed numerically lower body weight and abdominal fat weight. However, because the differences between the individual interventions and the combined treatment were not statistically significant, these findings should not be interpreted as evidence of a synergistic effect. Rather, they indicate that combining lutein with exercise was compatible with attenuation of HFD-induced adiposity. Whether lutein enhances the anti-obesity effects of exercise would require a study specifically designed to test an interaction between the two interventions.
The lipid profile provides further evidence of HFD-induced metabolic dysfunction. Rats in the HFD group had significantly higher TG, TC, and LDL levels together with lower HDL levels compared with controls, indicating marked dyslipidemia (Acikel Elmas et al., 2019; Baz et al., 2022). Our results revealed significantly higher LDL, TC, and TG levels and significantly lower HDL in the HFD group compared to the control group, which is compatible with (Acikel Elmas et al., 2019; Baz et al., 2022). Lutein supplementation and/or exercise significantly reduced LDL and TG and increased HDL relative to untreated HFD-fed rats. These changes indicate that both interventions improved lipid handling despite the persistence of HFD exposure. Lutein supplementation could reduce dyslipidemia and improve lipid profiles in HFD-fed rats (Narayanamurthy et al., 2018; Wang et al., 2021). further demonstrated reductions in circulating cholesterol and LDL-C following lutein supplementation in HFD-fed mice (Gopal et al., 2023). Also, lutein may activate nuclear receptors that control the expression of genes involved in lipid metabolism (Shamarao and Chethankumar, 2023; Sharoni et al., 2012). The present findings are consistent with these mechanisms, but direct pathway activation or inhibition cannot be concluded because gene and protein expression were not measured in this study. However, previous research revealed that abnormalities in lipid metabolism caused by HFD may be reversible with suitable exercise (Acikel Elmas et al., 2019; Y. Wang and Xu, 2017; Yang et al., 2016). A study by (Mika et al., 2019) reported that exercise increases lipolysis, reduces the uptake of fatty acids by adipocytes, alters the composition of fatty acids in adipose tissue, and modifies the expression of the enzymes responsible for the synthesis, elongation, and desaturation of fatty acids. Exercise also encourages the “beiging” of adipose tissue and helps to increase mitochondrial activity, which leads to a rise in fatty acid oxidation in the adipose tissue. The relatively low body weight and abdominal adiposity observed in the physical exercise groups are consistent with increased utilization of energy substrates during repeated exercise sessions. Recent evidence showing that exercise reduces visceral adipose tissue further supports this interpretation (Chen et al., 2024).
To confirm the biochemical assessment in this study, a histological analysis was performed. The examination of the longitudinal and transverse sections of the left ventricular wall of the HFD group revealed notable injuries in the waviness, disarrangement, and fragmentation of some cardiac muscle fibers with wider spaces between them. Also, congested blood vessels and inflammatory cell infiltration were seen. In addition, some cardiac muscle fibers showed pyknotic nuclei, while others showed hyaline degeneration. The results of several recent investigations emphasize the findings of this study, which showed that HFD could cause cardiac tissue damage in experimental animals (Feriani et al., 2021; Mabrouki et al., 2020; Shawky et al., 2019; Udomkasemsab and Prangthip, 2019). More recent experimental work has similarly demonstrated that HFD feeding can produce cardiac damage even in animals showing relative resistance to obesity, suggesting that cardiac injury is not determined solely by the magnitude of body weight (Feriani et al., 2021).
However, the examination of the longitudinal and transverse sections of the left ventricular wall of the lutein group showed nearly normal cardiac architecture with minimal damage, such as the waviness of some muscle fibers and congested blood vessels, compared to the control group. In addition, the examination of the longitudinal and transverse sections of the left ventricular wall of the HFD + Ph and HFD + L + Ph groups revealed a nearly normal histological structure, like that of the control group, with the restoration of histological changes. The findings of this study, which indicated that lutein could protect heart tissue from damage caused by HFD, are supported by the findings of previous studies (Han et al., 2015; Sharavana et al., 2017). Additionally, physical exercise has also been shown to ameliorate histological changes in the heart tissue induced by an HFD (Acikel Elmas et al., 2019; Sakr, 2013). Recent experimental evidence shows that swimming exercise can attenuate cardiac inflammation and histopathological injury in obese rats with metabolic dysfunction (Özüdoğru et al., 2023). These results may be explained by the fact that lutein and physical exercise enhance cardioprotection by exerting their antioxidant and anti-inflammatory effects.
5. Conclusion
The results of the present study revealed that lutein and physical exercise reduce body weight and caloric intake and significantly decrease abdominal fat accumulation that was increased in HFD-fed rats. Moreover, lutein and physical exercise considerably decreased fasting blood glucose and leptin levels, improved the lipid profile efficiently, and restored the normal histological structure of the heart. Overall, this study proved that lutein and physical exercise may be alternative approaches to managing obesity by effectively alleviating the metabolic changes caused by HFD. In addition, the study shows the effect of lutein and physical exercise on reducing the biochemical parameters, especially leptin and lipid profile. For future studies, we recommend increasing the duration of treatment to more than five weeks to determine the maximum synergetic effect that can be reached. Moreover, different doses of lutein and different types of exercise are recommended to be evaluated for other HFD complications. In general, obese rats develop many of the same key features as obese humans, such as insulin resistance, hyperglycemia, elevated fat stores, and chronic inflammation. These pathophysiological similarities make rats a useful model for exploring how obesity affects metabolism and heart health in humans, and to assess the response to dietary supplements and exercise. The combined intervention produced favorable outcomes across the measured variables, but the absence of statistically significant differences between combined and individual treatments prevents a conclusion of additive or synergistic action. Further studies examining insulin signaling, adipogenic pathways, mitochondrial function, oxidative stress, and inflammatory mediators in adipose and cardiac tissues would help clarify how lutein and exercise interact during HFD-induced obesity.
Acknowledgements
The authors would like to thank Badrah S. Algamdi and Mona H. Al-Thepyani, from the Pre-Clinical Research Unit at the King Fahad Medical Research Center, Jeddah, for their infrastructure and support. We would also like to thank the staff of King Fahd Medical Research Center, KAU, Jeddah, KSA, for their technical support.
Data Availability Statement
The original contributions presented in the study are included in the article, further inquiries can be directed to the corresponding author.
References
-
ABDUL KADIR, N.A.A., RAHMAT, A. and JAAFAR, H.Z.E., 2015. Protective effects of tamarillo (Cyphomandra betacea) extract against high fat diet induced obesity in Sprague-Dawley rats. Journal of Obesity, vol. 2015, pp. 846041. https://doi.org/10.1155/2015/846041 PMid:26171246.
» https://doi.org/10.1155/2015/846041 -
ACIKEL ELMAS, M., CAKICI, S.E., DUR, I.R., KOZLUCA, I., ARINC, M., BINBUGA, B., BINGOL OZAKPINAR, O., KOLGAZI, M., SENER, G. and ERCAN, F., 2019. Protective effects of exercise on heart and aorta in high-fat diet-induced obese rats. Tissue & Cell, vol. 57, pp. 57-65. https://doi.org/10.1016/j.tice.2019.01.005 PMid:30947964.
» https://doi.org/10.1016/j.tice.2019.01.005 -
AHN, Y.J., KIM, H., SCHMIDT, E., MOTOHASHI, H. and KIPP, A., 2021. Lutein as a modulator of oxidative stress-mediated inflammatory diseases. Antioxidants, vol. 10, no. 9, pp. 1448. https://doi.org/10.3390/antiox10091448 PMid:34573081.
» https://doi.org/10.3390/antiox10091448 - ALATAWI, M., BACKER, W. and BAZ, L., 2023 [viewed 4 March 2026]. The antioxidant and anti-inflammatory effects of lutein supplementation and physical exercise in heart tissue of obese male rats. Bioscience Research [online], vol. 20, no. 2, pp. 510-517. Available from: www.isisn.org
-
ALMESBEHI, T., HARRIS, L., MCGARTY, A., ALQALLAF, S., WESTROP, S., EDWARDS, C.A., DORLING, J.L. and MALKOVA, D., 2023. Effects of exercise training programmes on fasting gastrointestinal appetite hormones in adults with overweight and obesity: a systematic review and meta-analysis. Appetite, vol. 182, pp. 106424. https://doi.org/10.1016/j.appet.2022.106424 PMid:36565928.
» https://doi.org/10.1016/j.appet.2022.106424 -
AL-THEPYANI, M., ALGARNI, S., GASHLAN, H., ELZUBIER, M. and BAZ, L., 2022. Evaluation of the anti-obesity effect of zeaxanthin and exercise in HFD-induced obese rats. Nutrients, vol. 14, no. 23, pp. 4944. https://doi.org/10.3390/nu14234944 PMid:36500974.
» https://doi.org/10.3390/nu14234944 -
AMMAR, N.M., FARAG, M.A., KHOLEIF, T.E., METWALLY, N.S., EL-SHEIKH, N.M., EL GENDY, A.N. and ABDEL-HAMID, A.H.Z., 2017. Serum metabolomics reveals the mechanistic role of functional foods and exercise for obesity management in rats. Journal of Pharmaceutical and Biomedical Analysis, vol. 142, pp. 91-101. https://doi.org/10.1016/j.jpba.2017.05.001 PMid:28500980.
» https://doi.org/10.1016/j.jpba.2017.05.001 -
BAEK, K.-W., GIM, J.-A. and PARK, J.-J., 2020. Regular moderate aerobic exercise improves high-fat diet-induced nonalcoholic fatty liver disease via monoacylglycerol O-acyltransferase 1 pathway suppression. Journal of Sport and Health Science, vol. 9, no. 5, pp. 472-478. https://doi.org/10.1016/j.jshs.2018.09.001 PMid:32928450.
» https://doi.org/10.1016/j.jshs.2018.09.001 -
BAZ, L., ALGARNI, S., AL-THEPYANI, M., ALDAIRI, A. and GASHLAN, H., 2022. Lycopene improves metabolic disorders and liver injury induced by a hight-fat diet in obese rats. Molecules (Basel, Switzerland), vol. 27, no. 22, pp. 7736. https://doi.org/10.3390/molecules27227736 PMid:36431836.
» https://doi.org/10.3390/molecules27227736 -
BHANDARI, U., KUMAR, V., KHANNA, N. and PANDA, B.P., 2010. The effect of high-fat diet-induced obesity on cardiovascular toxicity in wistar albino rats. Human & Experimental Toxicology, vol. 30, no. 9, pp. 1313-1321. https://doi.org/10.1177/0960327110389499 PMid:21075806.
» https://doi.org/10.1177/0960327110389499 -
BLÜHER, M., 2019. Obesity: global epidemiology and pathogenesis. Nature Reviews. Endocrinology, vol. 15, no. 5, pp. 288-298. https://doi.org/10.1038/s41574-019-0176-8 PMid:30814686.
» https://doi.org/10.1038/s41574-019-0176-8 -
BLUNDELL, J.E., GIBBONS, C., CAUDWELL, P., FINLAYSON, G. and HOPKINS, M., 2015. Appetite control and energy balance: impact of exercise. Obesity Reviews : An Official Journal of the International Association for the Study of Obesity, vol. 16, suppl. 1, pp. 67-76. https://doi.org/10.1111/obr.12257 PMid:25614205.
» https://doi.org/10.1111/obr.12257 -
BOLLAPRAGADA, M.K., SHANTARAM, M. and R, S.K., 2017. Obesity: development, epidemiology, factors affecting, quantity, health hazards, management and natural treatment-a review. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 9, no. 2, pp. 12-26. https://doi.org/10.22159/ijpps.2017v9i2.15049
» https://doi.org/10.22159/ijpps.2017v9i2.15049 -
BOUTARI, C. and MANTZOROS, C.S., 2022. A 2022 update on the epidemiology of obesity and a call to action: as its twin COVID-19 pandemic appears to be receding, the obesity and dysmetabolism pandemic continues to rage on. Metabolism: Clinical and Experimental, vol. 133, pp. 155217. https://doi.org/10.1016/j.metabol.2022.155217
» https://doi.org/10.1016/j.metabol.2022.155217 -
CARPENTIER, S., KNAUS, M. and SUH, M., 2009. Associations between lutein, zeaxanthin, and age-related macular degeneration: an overview. Critical Reviews in Food Science and Nutrition, vol. 49, no. 4, pp. 313-326. https://doi.org/10.1080/10408390802066979 PMid:19234943.
» https://doi.org/10.1080/10408390802066979 -
CHEN, X., HE, H., XIE, K., ZHANG, L. and CAO, C., 2024. Effects of various exercise types on visceral adipose tissue in individuals with overweight and obesity: a systematic review and network meta‐analysis of 84 randomized controlled trials. Obesity Reviews : An Official Journal of the International Association for the Study of Obesity, vol. 25, no. 3, pp. e13666. https://doi.org/10.1111/obr.13666 PMid:38031812.
» https://doi.org/10.1111/obr.13666 -
CORRÊA, A.P.S., ANTUNES, C.F., FIGUEIRA, F.R., CASTRO, M.A., RIBEIRO, J.P. and SCHAAN, B.D., 2015. Effect of acute inspiratory muscle exercise on blood flow of resting and exercising limbs and glucose levels in type 2 diabetes. PLoS One, vol. 10, no. 3, pp. e0121384. https://doi.org/10.1371/journal.pone.0121384 PMid:25803283.
» https://doi.org/10.1371/journal.pone.0121384 -
EL ELJ, N., LAC, G., TABKA, Z., GHARBI, N. and EL FEZAA, S., 2011. Effect of physical exercise on reducing food intake and weight gain. Procedia: Social and Behavioral Sciences, vol. 30, pp. 2027-2031. https://doi.org/10.1016/j.sbspro.2011.10.392
» https://doi.org/10.1016/j.sbspro.2011.10.392 - FARMAN, M. and GHAFFAR, K., 2020. The impact of diet and exercise on diabetic patients. J. Med. Biol, vol. 2, no. 1, pp. 25-30.
-
FERIANI, A., BIZZARRI, M., TIR, M., ALDAWOOD, N., ALOBAID, H., ALLAGUI, M.S., DAHMASH, W., TLILI, N., MNAFGUI, K., ALWASEL, S. and HARRATH, A.H., 2021. High-fat diet-induced aggravation of cardiovascular impairment in permethrin-treated Wistar rats. Ecotoxicology and Environmental Safety, vol. 222, pp. 112461. https://doi.org/10.1016/j.ecoenv.2021.112461 PMid:34224971.
» https://doi.org/10.1016/j.ecoenv.2021.112461 -
FOCK, K.M. and KHOO, J., 2013. Diet and exercise in management of obesity and overweight. Journal of Gastroenterology and Hepatology, vol. 28, suppl. 4, pp. 59-63. https://doi.org/10.1111/jgh.12407 PMid:24251706.
» https://doi.org/10.1111/jgh.12407 -
FORNY-GERMANO, L., DE FELICE, F.G. and VIEIRA, M.N., 2019. The role of leptin and adiponectin in obesity-associated cognitive decline and Alzheimer’s disease. Frontiers in Neuroscience, vol. 12, pp. 1027. https://doi.org/10.3389/fnins.2018.01027 PMid:30692905.
» https://doi.org/10.3389/fnins.2018.01027 -
GHEIBI, S., KASHFI, K. and GHASEMI, A., 2017. A practical guide for induction of type-2 diabetes in rat: incorporating a high-fat diet and streptozotocin. Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie, vol. 95, pp. 605-613. https://doi.org/10.1016/j.biopha.2017.08.098
» https://doi.org/10.1016/j.biopha.2017.08.098 -
GOPAL, S.S., SUKHDEO, S.V., VALLIKANNAN, B. and PONESAKKI, G., 2023. Lutein ameliorates high‐fat diet‐induced obesity, fatty liver, and glucose intolerance in C57BL/6J mice. Phytotherapy Research : PTR, vol. 37, no. 1, pp. 329-341. https://doi.org/10.1002/ptr.7615 PMid:36086831.
» https://doi.org/10.1002/ptr.7615 -
GRIGG, M.J., THAKE, C.D., ALLGROVE, J.E., KING, J.A., THACKRAY, A.E., STENSEL, D.J., OWEN, A. and BROOM, D.R., 2023. Influence of water-based exercise on energy intake, appetite, and appetite-related hormones in adults: a systematic review and meta-analysis. Appetite, vol. 180, pp. 106375. https://doi.org/10.1016/j.appet.2022.106375 PMid:36375602.
» https://doi.org/10.1016/j.appet.2022.106375 -
GRONEK, P., WIELINSKI, D., CYGANSKI, P., RYNKIEWICZ, A., ZAJĄC, A., MASZCZYK, A., GRONEK, J., PODSTAWSKI, R., CZARNY, W., BALKO, S., CT CLARK, C. and CELKA, R., 2020. A review of exercise as medicine in cardiovascular disease: pathology and mechanism. Aging and Disease, vol. 11, no. 2, pp. 327-340. https://doi.org/10.14336/AD.2019.0516 PMid:32257545.
» https://doi.org/10.14336/AD.2019.0516 -
HAN, H., CUI, W., WANG, L., XIONG, Y., LIU, L., SUN, X. and HAO, L., 2015. Lutein prevents high fat diet-induced atherosclerosis in ApoE-deficient mice by inhibiting NADPH oxidase and increasing PPAR expression. Lipids, vol. 50, no. 3, pp. 261-273. https://doi.org/10.1007/s11745-015-3992-1 PMid:25663235.
» https://doi.org/10.1007/s11745-015-3992-1 -
HILLMAN, A.R., CULLUMS, L., PEAIRS, A. and MILLER, S.A., 2024. No difference in fat oxidation, postexercise energy expenditure or energy intake following ingestion of a protein-based breakfast compared to carbohydrate breakfast. Nutrition and Health https://doi.org/10.1177/02601060241241359 PMid:38545628.
» https://doi.org/10.1177/02601060241241359 - ISRAEL, P., CASTREJ, V., MANZANO-PECH, L. and GUARNER-LANS, V., 2021. Oxidative stress, plant natural antioxidants, and obesity. International Journal of Molecular Sciences, vol. 22, no. 1786, pp. 1-26.
-
JAKICIC, J.M. and OTTO, A.D., 2006. Treatment and prevention of obesity: what is the role of exercise? Nutrition Reviews, vol. 64, no. 2 Pt 2, pp. S57-S61. https://doi.org/10.1111/j.1753-4887.2006.tb00235.x PMid:16532900.
» https://doi.org/10.1111/j.1753-4887.2006.tb00235.x - KANG, Y.-S., KIM, J.-C., KIM, J.-S. and KIM, S.H., 2019. Effects of swimming exercise on serum irisin and bone FNDC5 in rat models of high-fat diet-induced osteoporosis. Journal of Sports Science & Medicine, vol. 18, no. 4, pp. 596-603. PMid:31827343.
-
KARRI, S., SHARMA, S., HATWARE, K. and PATIL, K., 2019. Natural anti-obesity agents and their therapeutic role in management of obesity: a future trend perspective. Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie, vol. 110, pp. 224-238. https://doi.org/10.1016/j.biopha.2018.11.076
» https://doi.org/10.1016/j.biopha.2018.11.076 -
KHALAFI, M., SAKHAEI, M.H., KHERADMAND, S., SYMONDS, M.E. and ROSENKRANZ, S.K., 2023. The impact of exercise and dietary interventions on circulating leptin and adiponectin in individuals who are overweight and those with obesity: a systematic review and meta-analysis. Advances in Nutrition, vol. 14, no. 1, pp. 128-146. https://doi.org/10.1016/j.advnut.2022.10.001 PMid:36811585.
» https://doi.org/10.1016/j.advnut.2022.10.001 -
KILANY, O.E., ABDELRAZEK, H.M.A., ALDAYEL, T.S., ABDO, S. and MAHMOUD, M.M.A., 2020. Anti-obesity potential of Moringa olifera seed extract and lycopene on high fat diet induced obesity in male Sprauge Dawely rats. Saudi Journal of Biological Sciences, vol. 27, no. 10, pp. 2733-2746. https://doi.org/10.1016/j.sjbs.2020.06.026 PMid:32994733.
» https://doi.org/10.1016/j.sjbs.2020.06.026 -
KIM, J.E., CLARK, R.M., PARK, Y., LEE, J. and FERNANDEZ, M.L., 2012. Lutein decreases oxidative stress and inflammation in liver and eyes of guinea pigs fed a hypercholesterolemic diet. Nutrition Research and Practice, vol. 6, no. 2, pp. 113-119. https://doi.org/10.4162/nrp.2012.6.2.113 PMid:22586499.
» https://doi.org/10.4162/nrp.2012.6.2.113 -
KOLIEB, E., MAHER, S.A., SHALABY, M.N., ALSUHAIBANI, A.M., ALHARTHI, A., HASSAN, W.A. and EL-SAYED, K., 2022. Vitamin D and swimming exercise prevent obesity in rats under a high-fat diet via targeting FATP4 and TLR4 in the liver and adipose tissue. International Journal of Environmental Research and Public Health, vol. 19, no. 21, pp. 13740. https://doi.org/10.3390/ijerph192113740 PMid:36360622.
» https://doi.org/10.3390/ijerph192113740 -
KOSTRYCKI, I.M., WILDNER, G., DONATO, Y.H., DOS SANTOS, A.B., BEBER, L.C.C., FRIZZO, M.N., LUDWIG, M.S., KEANE, K.N., CRUZAT, V., RHODEN, C.R. and HECK, T.G., 2019. Effects of high-fat diet on eHSP72 and extra-to-intracellular HSP70 levels in mice submitted to exercise under exposure to fine particulate matter. Journal of Diabetes Research, vol. 2019, pp. 1-13. https://doi.org/10.1155/2019/4858740 PMid:30723746.
» https://doi.org/10.1155/2019/4858740 -
LASKER, S., RAHMAN, M.M., PARVEZ, F., ZAMILA, M., MIAH, P., NAHAR, K., KABIR, F., SHARMIN, S.B., SUBHAN, N., AHSAN, G.U. and ALAM, M.A., 2019. High-fat diet-induced metabolic syndrome and oxidative stress in obese rats are ameliorated by yogurt supplementation. Scientific Reports, vol. 9, no. 1, pp. 20026. https://doi.org/10.1038/s41598-019-56538-0 PMid:31882854.
» https://doi.org/10.1038/s41598-019-56538-0 -
LAVIE, C.J., OZEMEK, C., CARBONE, S., KATZMARZYK, P.T. and BLAIR, S.N., 2019. Sedentary behavior, exercise, and cardiovascular health. Circulation Research, vol. 124, no. 5, pp. 799-815. https://doi.org/10.1161/CIRCRESAHA.118.312669 PMid:30817262.
» https://doi.org/10.1161/CIRCRESAHA.118.312669 -
LAZAR, J.M., KHANNA, N., CHESLER, R. and SALCICCIOLI, L., 2013. Swimming and the heart. International Journal of Cardiology, vol. 168, no. 1, pp. 19-26. https://doi.org/10.1016/j.ijcard.2013.03.063 PMid:23602872.
» https://doi.org/10.1016/j.ijcard.2013.03.063 -
LEVIN, B.E. and DUNN-MEYNELL, A.A., 2006. Differential effects of exercise on body weight gain and adiposity in obesity-prone and-resistant rats. International Journal of Obesity, vol. 30, no. 4, pp. 722-727. https://doi.org/10.1038/sj.ijo.0803192 PMid:16404411.
» https://doi.org/10.1038/sj.ijo.0803192 -
LI, H., HUANG, C., ZHU, J., GAO, K., FANG, J. and LI, H., 2018. Lutein suppresses oxidative stress and inflammation by Nrf2 activation in an osteoporosis rat model. Medical Science Monitor, vol. 24, pp. 5071-5075. https://doi.org/10.12659/MSM.908699 PMid:30030965.
» https://doi.org/10.12659/MSM.908699 -
LIU, M., LIU, H., XIE, J., XU, Q., PAN, C., WANG, J., WU, X., ZHENG, M. and LIU, J., 2017. Anti-obesity effects of zeaxanthin on 3T3-L1 preadipocyte and high fat induced obese mice. Food & Function, vol. 8, no. 9, pp. 3327-3338. https://doi.org/10.1039/C7FO00486A PMid:28848960.
» https://doi.org/10.1039/C7FO00486A -
MABROUKI, L., RJEIBI, I., TALEB, J. and ZOURGUI, L., 2020. Cardiac ameliorative effect of moringa oleifera leaf extract in high-fat diet-induced obesity in rat model. BioMed Research International, vol. 2020, no. 1, pp. 6583603. https://doi.org/10.1155/2020/6583603 PMid:32190675.
» https://doi.org/10.1155/2020/6583603 -
MIKA, A., MACALUSO, F., BARONE, R., DI FELICE, V. and SLEDZINSKI, T., 2019. Effect of Exercise on Fatty Acid Metabolism and Adipokine Secretion in Adipose Tissue. Frontiers in Physiology, vol. 10, pp. 26. https://doi.org/10.3389/fphys.2019.00026 PMid:30745881.
» https://doi.org/10.3389/fphys.2019.00026 -
MORELL, P. and FISZMAN, S., 2017. Revisiting the role of protein-induced satiation and satiety. Food Hydrocolloids, vol. 68, pp. 199-210. https://doi.org/10.1016/j.foodhyd.2016.08.003
» https://doi.org/10.1016/j.foodhyd.2016.08.003 -
MURASE, T., HARAMIZU, S., SHIMOTOYODOME, A. and TOKIMITSU, I., 2006. Reduction of diet-induced obesity by a combination of tea-catechin intake and regular swimming. International Journal of Obesity, vol. 30, no. 3, pp. 561-568. https://doi.org/10.1038/sj.ijo.0803135 PMid:16247510.
» https://doi.org/10.1038/sj.ijo.0803135 -
NAKHAEI, H., MOGHARNASI, M. and FANAEI, H., 2019. Effect of swimming training on levels of asprosin, lipid profile, glucose and insulin resistance in rats with metabolic syndrome. Obesity Medicine, vol. 15, pp. 100111. https://doi.org/10.1016/j.obmed.2019.100111
» https://doi.org/10.1016/j.obmed.2019.100111 -
NARAYANAMURTHY, U., ANANDHI, A. and MANIMEKALAI, K., 2018. Effect of lutein on lipid profile in hypercholesterolemic rats. International Journal of Basic and Clinical Pharmacology, vol. 7, no. 5, pp. 859-865. https://doi.org/10.18203/2319-2003.ijbcp20181625
» https://doi.org/10.18203/2319-2003.ijbcp20181625 -
NWACHUKWU, I.D., UDENIGWE, C.C. and ALUKO, R.E., 2016. Lutein and zeaxanthin: production technology, bioavailability, mechanisms of action, visual function, and health claim status. Trends in Food Science & Technology, vol. 49, pp. 74-84. https://doi.org/10.1016/j.tifs.2015.12.005
» https://doi.org/10.1016/j.tifs.2015.12.005 -
OHAROMARI, L.K., IKEMOTO, M.J., HWANG, D.J., KOIZUMI, H. and SOYA, H., 2021. Benefits of exercise and astaxanthin supplementation: are there additive or synergistic effects? Antioxidants, vol. 10, no. 6, pp. 870. https://doi.org/10.3390/antiox10060870 PMid:34071514.
» https://doi.org/10.3390/antiox10060870 -
OUYANG, B., LI, Z., JI, X., HUANG, J., ZHANG, H. and JIANG, C., 2019. The protective role of lutein on isoproterenol-induced cardiac failure rat model through improving cardiac morphology, antioxidant status via positively regulating Nrf2/HO-1 signalling pathway. Pharmaceutical Biology, vol. 57, no. 1, pp. 529-535. https://doi.org/10.1080/13880209.2019.1649436 PMid:31411934.
» https://doi.org/10.1080/13880209.2019.1649436 -
ÖZÜDOĞRU, E., ATAY, E., SAVRAN, M., AŞCI, H., ÖZMEN, Ö. and TOPSAKAL, Ş., 2023. Protective effects of swimming exercises and metformin on cardiac and aortic damage caused by a high-fat diet in obese rats with type 2 diabetes, by regulating the Bcl2/Bax signaling pathway. Turkish Journal of Medical Sciences, vol. 53, no. 6, pp. 1582-1592. https://doi.org/10.55730/1300-0144.5727 PMid:38813486.
» https://doi.org/10.55730/1300-0144.5727 -
PEDERSEN, B.K. and FEBBRAIO, M.A., 2012. Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nature Reviews. Endocrinology, vol. 8, no. 8, pp. 457-465. https://doi.org/10.1038/nrendo.2012.49 PMid:22473333.
» https://doi.org/10.1038/nrendo.2012.49 -
PERRONE, S., TEI, M., LONGINI, M. and BUONOCORE, G., 2016. The multiple facets of lutein: a call for further investigation in the perinatal period. Oxidative Medicine and Cellular Longevity, vol. 2016, pp. 5381540. https://doi.org/10.1155/2016/5381540 PMid:27668037.
» https://doi.org/10.1155/2016/5381540 -
PETRIDOU, A., SIOPI, A. and MOUGIOS, V., 2019. Exercise in the management of obesity. Metabolism: Clinical and Experimental, vol. 92, pp. 163-169. https://doi.org/10.1016/j.metabol.2018.10.009 PMid:30385379.
» https://doi.org/10.1016/j.metabol.2018.10.009 -
PIERINE, D.T., NAVARRO, M.E.L., MINATEL, I.O., LUVIZOTTO, R.A.M., NASCIMENTO, A.F., FERREIRA, A.L.A., YEUM, K.J. and CORRÊA, C.R., 2014. Lycopene supplementation reduces TNF-α via RAGE in the kidney of obese rats. Nutrition & Diabetes, vol. 4, no. 11, pp. e142. https://doi.org/10.1038/nutd.2014.39 PMid:25383746.
» https://doi.org/10.1038/nutd.2014.39 -
QIU, X., GAO, D.-H.H., XIANG, X., XIONG, Y.-F.F., ZHU, T.-S.S., LIU, L.-G.G., SUN, X.-F.F. and HAO, L.-P.P., 2015. Ameliorative effects of lutein on non-alcoholic fatty liver disease in rats. World Journal of Gastroenterology, vol. 21, no. 26, pp. 8061-8072. https://doi.org/10.3748/wjg.v21.i26.8061 PMid:26185377.
» https://doi.org/10.3748/wjg.v21.i26.8061 - RIAHI, F. and RIAHI, S., 2016. Effects of moderate swimming exercise on weight gain in high fat diet rats. Annals of Military and Health Sciences Research, vol. 14, no. 1, pp. 46-50.
- RIAZ, M., AHMAD, R., and ZIA-UL-HAQ, M., 2021. Carotenoids as antiobesity agents. In: M. ZIA-UL-HAQ, S. DEWANJEE and M. RIAZ. Carotenoids: structure and function in the human body Cham: Springer International Publishing, pp. 569-584.
-
RICHTER, E.A., BILAN, P.J. and KLIP, A., 2025. A comprehensive view of muscle glucose uptake: regulation by insulin, contractile activity, and exercise. Physiological Reviews, vol. 105, no. 3, pp. 1867-1945. https://doi.org/10.1152/physrev.00033.2024 PMid:40173020.
» https://doi.org/10.1152/physrev.00033.2024 -
ROCHA, G.L., CRISP, A.H., OLIVEIRA, M.R.M., SILVA, C.A., SILVA, J.O., DUARTE, A.C.G.O., SENE-FIORESE, M. and VERLENGIA, R., 2016. Effect of high intensity interval and continuous swimming training on body mass adiposity level and serum parameters in high-fat diet fed rats. TheScientificWorldJournal, vol. 2016, pp. 2194120. https://doi.org/10.1155/2016/2194120 PMid:26904718.
» https://doi.org/10.1155/2016/2194120 -
ROY, A. and PARKER, R.S., 2007. Dynamic modeling of exercise effects on plasma glucose and insulin levels. Journal of Diabetes Science and Technology, vol. 1, no. 3, pp. 338-347. https://doi.org/10.1177/193229680700100305
» https://doi.org/10.1177/193229680700100305 -
SAHRAOUI, A., DEWACHTER, C., VEGH, G., MC ENTEE, K., NAEIJE, R., BOUGUERRA, S.A. and DEWACHTER, L., 2020. High fat diet altered cardiac metabolic gene profile in Psammomys obesus gerbils. Lipids in Health and Disease, vol. 19, no. 1, pp. 123. https://doi.org/10.1186/s12944-020-01301-y PMid:32493392.
» https://doi.org/10.1186/s12944-020-01301-y - SAKR, H.F., 2013. Modulation of metabolic and cardiac dysfunctions by swimming in overweight rats on a high cholesterol and fructose diet: possible role of adiponectin. Journal of Physiology and Pharmacology, vol. 64, no. 2, pp. 231-240. PMid:23756398.
-
SAKURAI, T., OGASAWARA, J., KIZAKI, T., SATO, S., ISHIBASHI, Y., TAKAHASHI, M., KOBAYASHI, O., OH-ISHI, S., NAGASAWA, J., TAKAHASHI, K., ISHIDA, H., IZAWA, T. and OHNO, H., 2013. The effects of exercise training on obesity-induced dysregulated expression of adipokines in white adipose tissue. International Journal of Endocrinology, vol. 2013, pp. 801743. https://doi.org/10.1155/2013/801743 PMid:24369466.
» https://doi.org/10.1155/2013/801743 -
SALEM, S., 2015. Effect of two carotenoids (Lycopene and β-Carotene) supplementation on hyperlipidemia and lipid peroxidation in experimental albino rats. Journal of High Institute of Public Health, vol. 45, no. 1, pp. 1-7. https://doi.org/10.21608/jhiph.2015.20262
» https://doi.org/10.21608/jhiph.2015.20262 -
SCHUBERT, M.M., DESBROW, B., SABAPATHY, S. and LEVERITT, M., 2013. Acute exercise and subsequent energy intake. A meta-analysis. Appetite, vol. 63, pp. 92-104. https://doi.org/10.1016/j.appet.2012.12.010 PMid:23274127.
» https://doi.org/10.1016/j.appet.2012.12.010 -
SEO, M.J., SEO, Y.J., PAN, C.H., LEE, O.H., KIM, K.J. and LEE, B.Y., 2016. Fucoxanthin suppresses lipid accumulation and ROS production during differentiation in 3T3‐L1 adipocytes. Phytotherapy Research : PTR, vol. 30, no. 11, pp. 1802-1808. https://doi.org/10.1002/ptr.5683 PMid:27406217.
» https://doi.org/10.1002/ptr.5683 -
SHAMARAO, N. and CHETHANKUMAR, M., 2023. Molecular mechanism of anti-obesity effect of total lutein oxidized products (LOPs) in diet-induced obese mice. Journal of Taibah University for Science : JTUSCI, vol. 17, no. 1, pp. 2226489. https://doi.org/10.1080/16583655.2023.2226489
» https://doi.org/10.1080/16583655.2023.2226489 -
SHARAVANA, G., JOSEPH, G.S. and BASKARAN, V., 2017. Lutein attenuates oxidative stress markers and ameliorates glucose homeostasis through polyol pathway in heart and kidney of STZ-induced hyperglycemic rat model. European Journal of Nutrition, vol. 56, no. 8, pp. 2475-2485. https://doi.org/10.1007/s00394-016-1283-0 PMid:27488609.
» https://doi.org/10.1007/s00394-016-1283-0 -
SHARONI, Y., LINNEWIEL-HERMONI, K., KHANIN, M., SALMAN, H., VEPRIK, A., DANILENKO, M. and LEVY, J., 2012. Carotenoids and apocarotenoids in cellular signaling related to cancer: a review. Molecular Nutrition & Food Research, vol. 56, no. 2, pp. 259-269. https://doi.org/10.1002/mnfr.201100311 PMid:22102431.
» https://doi.org/10.1002/mnfr.201100311 -
SHAWKY, M.F., WAHBA, S.R. and HEIBASHY, M.I., 2019. Therapeutic Role of Coenzyme Q10 or/and α-lipoic acid on Cardiac Functions in Obese/Hypertensive Rats. Journal of Scientific Research in Science, vol. 36, no. 1, pp. 368-390. https://doi.org/10.21608/jsrs.2019.57636
» https://doi.org/10.21608/jsrs.2019.57636 - SINDHU, E.R., PREETHI, K.C. and KUTTAN, R., 2010. Antioxidant activity of carotenoid lutein in vitro and in vivo. Indian Journal of Experimental Biology, vol. 48, no. 8, pp. 843-848. PMid:21341544.
-
SLAOUI, M. and FIETTE, L., 2011. Histopathology procedures: from tissue sampling to histopathological evaluation. In: J.C. GAUTIER, eds. Drug safety evaluation: methods and protocols Totowa: Humana Press, vol. 691, pp. 69-82. https://doi.org/10.1007/978-1-60761-849-2_4
» https://doi.org/10.1007/978-1-60761-849-2_4 -
STONEHOUSE, W., WYCHERLEY, T., LUSCOMBE-MARSH, N., TAYLOR, P., BRINKWORTH, G. and RILEY, M., 2016. Dairy intake enhances body weight and composition changes during energy restriction in 18-50-year-old adults-a meta-analysis of randomized controlled Trials. Nutrients, vol. 8, no. 7, pp. 394. https://doi.org/10.3390/nu8070394 PMid:27376321.
» https://doi.org/10.3390/nu8070394 -
UDOMKASEMSAB, A. and PRANGTHIP, P., 2019. High fat diet for induced dyslipidemia and cardiac pathological alterations in Wistar rats compared to Sprague Dawley rats. Clínica e Investigación en Arteriosclerosis : Publicación Oficial de la Sociedad Española de Arteriosclerosis, vol. 31, no. 2, pp. 56-62. https://doi.org/10.1016/j.arteri.2018.09.004 PMid:30591270.
» https://doi.org/10.1016/j.arteri.2018.09.004 -
WANG, N., WANG, D., LUO, G., ZHOU, J., TAN, Z., DU, Y., XIE, H., LIU, L., YANG, X. and HAO, L., 2021. Lutein attenuates excessive lipid accumulation in differentiated 3T3-L1 cells and abdominal adipose tissue of rats by the SIRT1-mediated pathway. The International Journal of Biochemistry & Cell Biology, vol. 133, pp. 105932. https://doi.org/10.1016/j.biocel.2021.105932 PMid:33529717.
» https://doi.org/10.1016/j.biocel.2021.105932 -
WANG, Y. and XU, D., 2017. Effects of aerobic exercise on lipids and lipoproteins. Lipids in Health and Disease, vol. 16, no. 1, pp. 132. https://doi.org/10.1186/s12944-017-0515-5 PMid:28679436.
» https://doi.org/10.1186/s12944-017-0515-5 -
YANG, C., LI, L., YANG, L., LǙ, H., WANG, S. and SUN, G., 2018. Anti-obesity and Hypolipidemic effects of garlic oil and onion oil in rats fed a high-fat diet. Nutrition & Metabolism, vol. 15, no. 1, pp. 43. https://doi.org/10.1186/s12986-018-0275-x PMid:29951108.
» https://doi.org/10.1186/s12986-018-0275-x - YANG, X.Q., YUAN, H., LI, J., FAN, J.J., JIA, S.H., KOU, X.J. and CHEN, N., 2016. Swimming intervention mitigates HFD-induced obesity of rats through PGC-1α-irisin pathway. European Review for Medical and Pharmacological Sciences, vol. 20, no. 10, pp. 2123-2130. PMid:27249613.
-
ZALAQI, Z., GHAZALIAN, F., KHODAYAR, M.J., RAESI VANANI, A., KHORSANDI, L. and SHUSHIZADEH, M.R., 2022. Swimming training combined with chitosan supplementation reduces the development of obesity and oxidative stress in high-fat diet-fed mice. The British Journal of Nutrition, vol. 127, no. 6, pp. 837-846. https://doi.org/10.1017/S0007114521001379 PMid:33902761.
» https://doi.org/10.1017/S0007114521001379 -
ZHOU, J., WANG, S., WANG, Q., ZHAO, R., WANG, D., XIE, H., DU, Y., XU, Y., DENG, J., HUANG, Y., LIU, Y., PENG, X., HAO, L. and LIU, L., 2025. Effect of lutein supplementation on blood lipids and advanced glycation end products in adults with central obesity: a double-blind randomized controlled trial. Food & Function, vol. 16, no. 5, pp. 2096-2107. https://doi.org/10.1039/D4FO05578K PMid:39964702.
» https://doi.org/10.1039/D4FO05578K
*
e-mail: lbaz@kau.edu.saEditor:
