EXERCISE AND SEX IMPACT HEPATIC BILE ACID METABOLISM AND FECAL EXCRETION

Abstract

Exercise can improve metabolic outcomes associated with obesity including hepatic steatosis, however, precise mechanisms are not fully established, nor is the impact of sex. In this study we tested the hypothesis that exercise (via voluntary wheel running (VWR)) would increase expression of hepatic genes controlling cholesterol (Chol) and bile acid (BA) synthesis, and increase fecal BA excretion in male and female C57BL/6 mice providing a mechanism for diverting hepatic acetyl‐CoA away from de novo lipogenesis and towards fecal excretion. A time restricted feeding paradigm was also examined because nutrient availability (fed vs. fasting) impacts the Chol/BA pathway and may impact the capacity for VWR to modulate liver metabolism. Male and female, eight‐week old mice were randomly assigned to one of the following treatment groups (n = 8/group) while consuming a chow diet: sedentary plus ad libitum access to food (SED‐AL), sedentary plus overnight food restricted (SED‐OFR), voluntary wheel running ad libitum access to food (VWR‐AL), and voluntary wheel running plus overnight food restricted (VWR‐OFR) for a period of 4 weeks. Additionally, half of the mice in each group were either fed or fasted immediately prior to tissue collection. Females displayed across the board higher fecal bile acid concentration and higher hepatic gene expression for ACLY, CYP7A1, HMGCR, and FXR compared to males regardless of treatment condition. VWR only increased fecal BA concentration in fed females (VWR‐AL) while the effects of VWR and feeding status on hepatic expression of ACLY, CYP7a1, and HMGCR were mixed and largely insignificant compared to the male vs. female differences. Females had lower serum cholesterol and triglyceride levels. Exercise reduces susceptibility for hepatic steatosis, and female rodents are known to be protected against steatosis and these results suggest that these effects are associated with increased fecal BA excretion and/or an upregulation of Chol/BA synthesis gene expression.Support or Funding InformationVA Merit Review grant (1I01BX002567‐01) (JPT)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.