(P04-035-25) Lack of Soluble Fiber Impairs Metabolic Flexibility and Nocturnal Pattern of Activities

Objectives: Previous studies have shown that compositionally defined diet (CDD), made from purified ingredients, increases adiposity and promotes metabolic syndrome compared to normal chow diet (NCD), which is composed of relatively unrefined plant and animal products. A major difference between CDD and NCD is the use of non-fermentable cellulose as the sole fiber source in CDD, while NCD contains mixed fibers. Earlier research has shown impaired metabolic flexibility as a hallmark of metabolic dysfunction; however, whether soluble, fermentable fibers affect metabolic flexibility is not known. 

The goal of this study was to investigate the extent to which metabolic fitness is driven by dietary fibers.

Methods: In the first cohort, adult C57BL/6J mice (12 weeks of age) were maintained on NCD (Teklad 2018) or CDD (D12450J, Research Diets) for 8 weeks on 12h/12h light/dark cycles. In the second cohort, adult C57BL/6J mice were subjected to cellulose-containing or inulin (a soluble fiber)-containing semi-purified diets for 8 weeks; the diets are matched in fiber content to eliminate potential bulking effects. Both cohorts were subjected to indirect calorimetry and SCFA analyses.

Results: Mice on NCD showed distinct nocturnal pattern of increased physical activities, energy expenditure and respiratory exchange ratio (RER) during dark phase compared to light phase; this circadian pattern was disrupted in CDD-fed mice. RER provides a measure of metabolic flexibility, which refers to the body’s ability to adapt fuel oxidation to fuel availability, efficiently switching between carbohydrates and fats based on dietary intake and energy demands. Notably, inulin-diets restored the nocturnal pattern of RER. Fecal analysis of short chain fatty acids (SCFAs) showed a marked decrease in SCFAs in CDD-fed mice compared to NCD-fed mice, and the levels were restored by inulin-containing diets.

Conclusions: Our data suggest that the fermented microbial metabolites SCFAs contribute to overall metabolic flexibility of the host, lending further support to the evidence that lack of soluble fiber contributes to metabolic dysfunction in mice.

Funding Sources: This work was supported in part by the National Institute of Environmental Health Sciences and Institute of Advancing Health Through Agriculture to C.-S. Wu.