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ARS Home » Southeast Area » Little Rock, Arkansas » Arkansas Children's Nutrition Center » Research » Publications at this Location » Publication #360067
Title: Weight loss and fitness intervention increases markers of hepatic bile acid (BA) synthesis, while reducing serum total BA concentrations in sedentary, obese insulin resistant women

Author
item MERCER, KELLY - Arkansas Children'S Nutrition Research Center (ACNC)
item LOU, XIANGYANG - Arkansas Children'S Nutrition Research Center (ACNC)
item PACK, LINDSAY - University Arkansas For Medical Sciences (UAMS)
item THYFAULT, JOHN - University Of Arkansas
item CAMPBELL, CAITLIN - Former ARS Employee
item GRAPOV, DMITRY - University Of California, Davis
item OLIVER, FIEHN - Barenbrug West Coast Research Station
item CHANDLER, CAROL - Former ARS Employee
item BURNETT, DUSTIN - Former ARS Employee
item SOUZA, ELAINE - Former ARS Employee
item CASAZZA, GRETCHEN - University Of California, Davis
item Gustafson, Mary
item Keim, Nancy
item Newman, John
item HUNTER, GARY - University Of Alabama
item FERNANDEZ, JOSE - University Of Alabama
item GARVEY, TIMOTHY - University Of Alabama
item HARPER, MARY-ELLEN - University Of Ottawa
item HOPPEL, CHARLES - Case Western Reserve University (CWRU)
item MEISSEN, JOHN - University Of California, Davis
item TAKE, KOHEI - University Of California, Davis
item 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.