Divergence in aerobic capacity impacts bile acid metabolism in young women

Authors: MAURER, ADRIANNA - University Of Kansas; WARD, JAIMIE - University Of Kansas; DEAN, KELSEY - University Of Arkansas; BILLINGER, SANDRA - University Of Kansas; LIN, HAIXA - Arkansas Children'S Nutrition Research Center (ACNC); MERCER, KELLY - Arkansas Children'S Nutrition Research Center (ACNC); Ferruzzi, Mario; THYFAULT, JOHN - University Of Kansas

Submitted to: Journal of Applied Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/25/2020
Publication Date: 8/27/2020
Citation: Maurer, A., Ward, J., Dean, K., Billinger, S.A., Lin, H., Mercer, K.E., Adams, S.H., Thyfault, J. 2020. Divergence in aerobic capacity impacts bile acid metabolism in young women. Journal of Applied Physiology. 129(4):768-778. https://doi.org/pubmed.ncbi.nlm.nih.gov/32853107/.

Interpretive Summary: High aerobic capacity and regular physical activity have profound effects on energy metabolism. Their influence on bile acid (BA) metabolism has been proven in rodents, but the relevance of these findings to human health is unknown. In the current study, apparent differences in BA metabolism between women with contrasting exercise and aerobic capacity levels were found, although no differences in BA synthesis. Women with low aerobic capability (Lo-Fit) had a sustained increase in circulating conjugated BAs post an Oral Glucose Tolerance Test (OGTT) in postprandial condition, while women with high aerobic capacity (Hi-Fit) showed only a transient increase. Additionally, Hi-Fit women showed sustained elevations of the secondary BA, lithocholic acid (LCA) during the OGTT, not seen in the Lo-Fit women. The results indicate that the differences in exercise and aerobic capacity do lead to changes in BA metabolism and postprandial circulating concentrations of select BA species. The differences in circulating BA components between Hi- and Lo-Fit women could contribute to their differences in insulin sensitivity and energy regulation, via different signaling mechanisms. It will provide new insight into a better understanding of the roles of BA metabolism in mediating metabolic health associated with exercise and aerobic capacity.

Technical Abstract: Liver adaptations may be critical for regular exercise and high aerobic capacity to protect against metabolic disease, but mechanisms remain unknown. Bile acids (BAs) synthesized in the liver are bioactive and can putatively modify energy metabolism. Regular exercise influences BA metabolism in rodents but effects in humans are unknown. This study tested if female subjects screened for high aerobic capacity (Hi-Fit, n=19) (VO2peak>=45 mL/kg/min) have increased hepatic BA synthesis and different circulating BA composition compared to those matched for age and body mass with low aerobic capacity (Lo-Fit, n=19) (VO2peak<=35 mL/kg/min). Diet patterns, activity level, stool, and blood were collected at baseline before receiving a 1-week standardized, eucaloric diet. After the 1-week standardized diet, stool and blood were again collected, and an Oral Glucose Tolerance Test (OGTT) was performed to assess insulin sensitivity and postprandial BA response. Contrary to our hypothesis, serum 7a-hydroxy-4-cholesten-3-one (C4), a surrogate of BA synthesis was not different between groups while Hi-Fit women had lower fecal BA concentrations compared to Lo-Fit. However, Lo-Fit women had a higher and more sustained rise in circulating conjugated BAs during the OGTT. Hi-Fit women showed a significant post-OGTT elevation of the secondary BA, lithocholic acid (LCA), a potent TGR5 agonist, in contrast to Lo-Fit where no response was observed. A one-week control diet eliminated most differences in circulating BA species between groups. Overall, the results emphasize the importance of using a standardized diet when evaluating BAs and indicate that regular exercise and aerobic capacity modulate BA metabolism under postprandial conditions. Women with contrasting exercise and aerobic capacity levels show clear differences in bile acid (BA) metabolism. Women with low aerobic capacity (Lo-Fit) have increased circulating conjugated BAs post oral glucose tolerance test (OGTT), whereas women with high aerobic capacity (Hi-Fit) display a transient increase. Hi-Fit women show an increase in the secondary BA, lithocholic acid, during the OGTT not seen in Lo-Fit women. Differences in circulating BA species between Hi- and Lo-Fit women possibly contribute to differences in insulin sensitivity and energy regulation via different signaling mechanisms.