Combined Lutein and Exercise Intervention Alleviates Brain Alteration Induced by a High-Fat Diet in Obese Rats

Obesity is a major global health issue, causing many diseases in organs like the liver, heart, and brain. Diverse strategies, including dietary interventions and regular exercise, are potential strategies to combat obesity and its obesogenic consequences on the brain. Natural products like carotenoids such as lutein (Lu) have several positive impacts on human health and can help in reducing obesity. This study aimed to evaluate the combined effects of lutein supplementation and physical exercise (PE) on metabolic and hippocampal alterations associated with obesity. Wistar rats were fed a standard diet as a negative control group, and the other group was fed a high-fat diet (HFD) for 12 weeks. Then, obese rats were randomly divided into four groups based on the following treatments: (i) a HFD only, (ii) a high-fat diet supplemented with lutein (HFD + Lu), (iii) a high-fat diet plus physical exercise (HFD + PE), (iv) a high-fat diet plus a combination of lutein and physical exercise (HFD + Lu + PE) for another 5 weeks. By the end of Week 17, all groups went through a behavioral test (Y-maze), and blood samples, visceral and brain tissues were collected for biochemical and histological examinations, respectively. Our results showed that combining Lu and PE significantly reduced blood glucose, lipid profile parameters, leptin, and malondialdehyde (MDA) levels compared with the HFD group (all p < 0.0001). Furthermore, the HFD + Lu + PE group exhibited significantly higher levels of high-density lipoprotein (HDL-C), catalase (CAT), and superoxide dismutase (SOD), along with significantly lower levels of interleukin-6 (IL-6) compared with the HFD group (all p < 0.0001). Treatments with Lu, PE, and Lu + PE significantly enhanced short-term spatial memory performance in the Y-maze (p < 0.001) and attenuated hippocampal histopathological alterations compared with the HFD group. This study demonstrated that combining lutein and physical exercise is an alternate approach for improving brain health and preventing obesity and its complications in rats fed with HFD. Additionally, the combination of Lu and PE had more beneficial effects on the rat's brain than either Lu or PE alone.