Voluntary Exercise Differentially Affects High-Fat Induced Metabolic Phenotypes Across BXD Mouse Strains

A recent study has uncovered how voluntary exercise can influence metabolic phenotypes in mice subjected to a high-fat diet. Researchers examined three specific BXD mouse strains, BXD40, BXD43, and BXD100, which showed a predisposition to engage in voluntary wheel-running, covering approximately 6 kilometers daily within a 24-week period.

Despite starting with around 9 kilometers per day during the initial two weeks, the wheel usage stabilized at around 5 kilometers per day, yet the exercise still managed to boost oral glucose tolerance by 35% compared to sedentary mice by 24 weeks.

Interestingly, the mice that exercised consumed 20% more food relative to their body weight, indicating the glucose benefits were not solely due to increased caloric intake. The researchers then investigated whether the gut microbiome played a role in this positive metabolic effect. They found that even though long-term exercise led to slight, strain-dependent shifts in the bacterial composition of the cecum, it also caused functional changes associated with carbohydrate and glucose metabolism.

By exchanging bedding between sedentary and running BXD43 mice, they were able to reduce the differences in microbial communities, leading to a significant improvement in the glucose phenotype without any change in the exercise behavior. Overall, this research confirms the BXD40, BXD43, and BXD100 strains as excellent models for exploring how diet, exercise, and genetic factors interact in the development of metabolic diseases, and highlights the potential influence of certain gut microbial taxa on the metabolic benefits derived from exercise during a high-fat feeding regimen.