Interaction between exercise and flaxseed oil intake on hippocampal function of obese mice: the case of GPR120

Obesity and physical inactivity are recognized as modifiable risk factors for dementia. Therefore, nutrition and exercise training play a pivotal role in cognitive function. However, how nutrients interact with exercise to enhance each other's beneficial effects on the central nervous system in obesity is understudied in the scientific literature. Here, we explored the interaction between flaxseed oil, a vegetable source of omega-3 (ω3) fatty acid (alpha-linolenic [ALA] - C18:3), and aerobic exercise training on the hippocampal function of a diet-induced obesity mouse model, focusing on the ω3 receptor GPR120. After 12 weeks on a high-fat diet (HF), mice exhibited a classic obesity phenotype characterized by increased body weight, adipose tissue, and elevated fasting blood glucose. Four weeks of aerobic treadmill running mitigated the weight gain from the HF. However, only when combined with flaxseed oil intake did glucose metabolism improve. Obese mice also exhibited anxiety behavior, followed by a higher content of hippocampal GPR120, more specifically in the inner zone of the dentate gyrus. Without changes in hippocampal GPR120 content and inflammatory markers, exercise training combined with flaxseed oil intake mildly reduced anxiety parameters. Thus, the obesity condition seems to increase anxiety and the ω3 receptor in the hippocampus, making it an interesting target for understanding obesity-induced cognitive decline. Furthermore, four weeks of combining flaxseed oil intake with exercise training appear insufficient to improve hippocampal function in the context of obesity.