Identification of gut-derived factors responsible for
exercise-reward, physical inactivity and obesity
(SUOLI)

Main funder

Research Council of Finland

Funder's project number: 349264

Funds granted by main funder (€)

499 865,00

Funding program

Academy Project, AoF (Research Council of Finland)

Project timetable

Project start date: 01/09/2022

Project end date: 31/08/2026

Summary

Although physical inactivity and obesity are increasing world-wide and creating major health problems, the intimate causes of the complex syndrome are not well known. Exercise could be an effective way to combat obesity, but it is not fully understood why many individuals do not lose fat mass upon exercising. Our previous animal studies have suggested that the gut microbiota (GM) can modulate obesity and physical activity, which may be linked to brain reward signaling e.g., via GM-produced metabolites. In this proposed study, we will evaluate the role of GM, diet, and the GM-metabolites in exercise-reward and physical activity. Understanding of the GM species that produce major bioactive metabolites could lead to therapeutic strategies using specific diets targeting the GM. Our unique opportunity to work together with the only Exercise Medicine Outpatient Clinic in Finland ensures translating our findings from mechanisms to practice, thus increasing the social impact of our research.
To thoroughly explore whether the same phenomena seen in animals associate with obesity and inactivity also in humans, we will study obese patients that are treated with personalized exercise. First, 1) we will study how patient’s GM, metabolites and fat mass respond to exercise, and conversely, what characterizes those patients whose do not. After that, 2) we will identify, which factors, including GM, GM-metabolites and diet play a role in exercise-induced fat mass loss and reward. Then, 3) we will make a GM transplantation study using feces from obese patients who lost/did not lose fat mass and got/did not get reward from exercise during training and transfer the feces to obese mice. The purpose is to find out to what extent GM and their metabolites affect physical activity, reward and obesity.
The major scientific breakthrough will be in identifying the GM and their metabolites responsible for exercise reward, which may explain the variation in the outcomes when obese patients practice exercise. The study will give new insights to the recently recognized gut-brain axis, so that obesity could be better understood and tackled. In addition to scientific goals, the study can provide applications in diagnostic field by revealing new metabolic biomarkers for healthy and disease-related GM, and in therapeutic field by providing new therapeutic options for obesity management by modulating the GM or the diet affecting the GM.