Research Sebastiaan Dalle

Abstract

Obesity and related metabolic disorders present significant global health challenges. Current treatments for obesity focus on weight loss but can result in unintended lean mass loss, which negatively impact overall health. While exercise is known to improve muscle quality and metabolism, and to reduce inflammation, the underlying mechanisms driving these beneficial effects remain poorly understood. The endocannabinoid system (ECS), which includes bioactive lipids such as anandamide, plays a key role in regulating metabolism and inflammation. Dysregulation of the ECS has been implicated in metabolic disturbances, particularly in obesity. However, the precise role of the ECS in exercise-induced adaptations, particularly in the context of obesity, remains unclear. This project aims to investigate the influence of the ECS on metabolic and inflammatory responses to endurance exercise in obesity. The objectives of this research are designed to fill critical gaps in our understanding of the ECS's role in exercise adaptation and its potential for therapeutic intervention. The research is structured around four primary aims: 1. Identification of tissues contributing to exercise-induced increases in eCB levels. This aim will involve examining the tissue-specific response of the ECS to exercise and determining which tissues contribute most significantly to the observed changes in eCB levels. 2. Examination of the effects of diet-induced obesity on eCB responses to acute exercise. This aim will investigate how obesity influences the exercise-induced modulation of the ECS, and how this related to metabolic and inflammatory regulators. 3. Restoration of eCB responses to acute exercise in obese mice. This aim will examine whether restoring eCB responses to acute exercise in obesity can enhance metabolic and inflammatory adaptations. The research will involve pharmacologically modulating the ECS to restore its activity and observing the effects on exercise-induced changes in metabolic and inflammatory regulators. 4. Evaluation of the effects of restored ECS responses during chronic exercise training on obesity-related metabolic, inflammatory, and fitness outcomes. The final aim will investigate whether the restoration of eCB function during chronic exercise training enhances long-term metabolic and inflammatory adaptations. It is hypothesized that improved ECS activity during exercise training will amplify the beneficial effects of exercise, particularly in obese mice, by enhancing both inflammatory, metabolic health and fitness levels. The research will utilize a high-fat, high-fructose diet-induced obesity model in mice to simulate the metabolic disturbances associated with obesity. A combination of molecular analyses, metabolic testing, and pharmacological interventions will be employed to assess eCB levels and activity, as well as their relationship with key metabolic and inflammatory regulators. The study will also explore how these interventions influence exercise performance and adaptations to both acute and chronic endurance exercise. Ultimately, the results of this study have the potential to provide valuable insights into the role of the ECS in exercise adaptations and metabolic health. By identifying ways to modulate the ECS to enhance exercise-induced benefits, this research could inform the development of new therapeutic strategies for improving metabolic health in individuals with obesity and related disorders. Through its investigation into the interplay between exercise, inflammation, metabolism, and the ECS, this research could provide a foundational basis for future interventions aimed at improving health outcomes in obesity and other metabolic disorders.

Researcher(s)

• Promoter: Dalle Sebastiaan

Research team(s)

• Movement Antwerp (MOVANT)

Project type(s)

• Research Project