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Research Project: Impact of Early Dietary Factors on Child Development and Health

Location: Arkansas Children's Nutrition Center

Title: Gut microbiota are linked to increased susceptibility to hepatic steatosis in low aerobic capacity rats fed an acute high fat diet

item PANASEVICH, M - University Of Missouri
item MORRIS, E - University Of Kansas Medical School
item CHINTAPALLI, S - Arkansas Children'S Nutrition Research Center (ACNC)
item WANKHADE, U - Arkansas Children'S Nutrition Research Center (ACNC)
item SHANKAR, K - Arkansas Children'S Nutrition Research Center (ACNC)
item BRITTON, S - University Of Michigan
item KOCH, L - University Of Michigan
item THYFAULT, J - University Of Kansas Medical School
item RECTOR, R - University Of Missouri

Submitted to: American Journal of Physiology - Gastrointestinal and Liver Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/2/2016
Publication Date: 6/10/2016
Citation: Panasevich, M.R., Morris, E.M., Chintapalli, S.V., Wankhade, U.D., Shankar, K., Britton, S.L., Koch, L.G., Thyfault, J.P., Rector, R.S. 2016. Gut microbiota are linked to increased susceptibility to hepatic steatosis in low aerobic capacity rats fed an acute high fat diet. American Journal of Physiology - Gastrointestinal and Liver Physiology. 311(1):G166-G179. doi: 10.1152/ajpgi.00065.2016.

Interpretive Summary: Poor fitness is a strong predictor of worse overall health and susceptibility to disease. However, how having low fitness (also measured as aerobic capacity) promotes susceptibility to disease, especially accumulation of fat in the liver is poorly understood. By employing rats that intrinsically have highly divergent capacity to run (which translates to greater fitness), we examined the response of low and high fit animals to a short (3 day) challenge to diets high in calories from fat. Since one important component of diet associated effects may be mediated via reconfiguration of the gut microbiome, we examined the ecology of gut microbiota in these rats. Findings from these analyses revealed that rats with high running capacity had lower accumulation of fats in the liver associated with changes in the composition of specific bacterial classes. Animals with lower fitness also showed greater abundance of bacteria involved in processing sugars for energy. These studies allude towards a complex interaction between intrinsic aerobic fitness, microbiome membership and metabolic health. In the future, these findings may enhance our ability to manipulate metabolic diseases via uncovering links between exercise, fitness and the microbiome.

Technical Abstract: Poor aerobic fitness is linked to nonalcoholic fatty liver disease and increased all-cause mortality. We previously found that low capacity running (LCR) rats fed acute high fat diet (HFD; 45% kcal from fat) for 3 days resulted in positive energy balance and increased hepatic steatosis compared with high aerobically fit, high capacity running (HCR) rats. Here, we tested the hypothesis that poor physiological outcomes in LCR rats following acute HFD feeding are associated with alterations in cecal microbiota. LCR rats exhibited greater body weight, feeding efficiency, 3 d body weight change, and liver triglycerides after acute HFD feeding compared with HCR rats. Furthermore, LCR rats exhibited reduced expression of intestinal tight junction proteins compared with HCRs. Cecal bacterial 16S rDNA revealed that LCR rats had reduced cecal Proteobacteria compared with HCR rats. Microbiota of HCR rats had greater, Desulfovibrionaceae, unassigned genera within Desulfovibrionaceae, suggesting increased reduction of endogenous mucins and proteins. While acute HFD feeding reduced Firmicutes in both strains, short-chain fatty acid-producing Phascolarctobacterium was reduced in LCR rats. In addition, Ruminococcae and Ruminococcus were negatively correlated with energy intake in the LCR/HFD rats. Predicted metagenomic function suggests that LCR rats have a greater metabolic capacity to metabolize carbohydrate and energy compared with HCR rats. Overall, these data suggest that the populations and metabolic capacity of the microbiota in low aerobically fit LCR rats may contribute to their susceptibility to acute HFD-induced hepatic steatosis and poor physiologic outcomes.