Author
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MERCER, KELLY - Arkansas Children'S Nutrition Research Center (ACNC) |
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LOU, XIANGYANG - Arkansas Children'S Nutrition Research Center (ACNC) |
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PACK, LINDSAY - University Arkansas For Medical Sciences (UAMS) |
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THYFAULT, JOHN - University Of Arkansas |
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CAMPBELL, CAITLIN - Former ARS Employee |
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GRAPOV, DMITRY - University Of California, Davis |
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OLIVER, FIEHN - Barenbrug West Coast Research Station |
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CHANDLER, CAROL - Former ARS Employee |
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BURNETT, DUSTIN - Former ARS Employee |
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SOUZA, ELAINE - Former ARS Employee |
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CASAZZA, GRETCHEN - University Of California, Davis |
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Gustafson, Mary |
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Keim, Nancy |
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Newman, John |
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HUNTER, GARY - University Of Alabama |
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FERNANDEZ, JOSE - University Of Alabama |
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GARVEY, TIMOTHY - University Of Alabama |
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HARPER, MARY-ELLEN - University Of Ottawa |
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HOPPEL, CHARLES - Case Western Reserve University (CWRU) |
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MEISSEN, JOHN - University Of California, Davis |
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TAKE, KOHEI - University Of California, Davis |
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Ferruzzi, Mario |
Submitted to: Meeting Abstract
Publication Type: Abstract Only Publication Acceptance Date: 1/31/2019 Publication Date: N/A Citation: N/A Interpretive Summary: Technical Abstract: Beyond adipose and muscle, excerise has profound effects in other metabolically-important tissues including the liver. Bile acids (BAs) are synthesized from cholesterol via the rate-limiting enzyme Cholesterol 7 alpha-hydroxylase (CYP7A1) and contribute to the solubilzation and absorption of lipid soluble nutrients, and serve as important signaling molecules capable of systemic endocrine function. Circulating BA are known to increase with obesity and insulin resistance, but effects following exercise and diet induced weight loss are unknown. To test if improved fitness and weight loss influence bile acid metabolism and homeostasis, we measured fasting serum concentrations of total BAs (conjugated and free forms of primary and secondary BAs) in sedentary, obese insulin-resistant women (N=12) before and after a ~14 wk weight loss and exercise intervention [Campell et al. 2014, PLoS One, 9: e84260]. In addition, serum FGF19 (a regulator of BA synthesis) and 7-alpha-hydroxy-cholesten-3-one (C4, a verified marker of CYP7A1 enzymatic acitivity) were measured by ELISA and LC-MS, respectively. Using mixed-model analyses and the change in relative VO2peak (mL/min/kg) as a covariate, we observed a significant decrease (~30%) in total serum BAs post-intervention relative to pre-intervention samples. Corresponding to the decrease in total BAs, fasting serum concentrations of C4 were 55% higher post-intervention relative to the matched pre-intervention samples (P=0.004). Interestingly, we observed no changes in serum FGF19. These data suggest that exercise may drive increased BA metabolism marked by increased hepatic BA synthesis and reduces serum BA. The underlying mechanisms remain to be determined, but work from our preclinical rodent models suggest that increased BA metabolic flux may be linked to enhanced hepatic mitochondrial function. |