Sex Differentiation in the Bile Acid Pathway

Overview

Bile acid (BA) sequestering drugs, usually prescribed to lower cholesterol, have been shown to reduce liver triglycerides in mouse models highlighting a possible pharmaceutical treatment for non-alcoholic fatty liver disease (NAFLD), an increasingly prevalent condition in which >5% of the liver weight is comprised of lipid stores. This is crucial as current NAFLD treatment recommendations are limited to diet and exercise, with no pharmaceutical interventions available. Instances of NAFLD are increasing worl dwide with 30% of the population affected. Critical to this study, there are significant sex differences in NAFLD prevalence with females experiencing a lowered risk of NAFLD until menopause when estrogen signaling is lost, highlighting the protective effe cts of estrogen. Estrogens enact transcriptional effects through receptors. Estrogen receptor alpha (ERɑ) is the primary estrogen receptor in the liver. Investigating the role that ERɑ plays in NAFLD manifestation, and the significance of the BA pathway in liver health could lead to new treatment developments. Our data reveals several significant sex differences in the BA pathway in response to BA - sequestering drugs. BA sequestrants increased transcription of ER ɑ in wild -type (WT) female mice uncovering a possible female protective mechanism to metabolic stress. BA sequestrants increased fecal BA concentration in only female mice and fecal calories in only male mice, displaying dimorphic responses to the drug. Ad ditionally, ERɑ does not play a critical role in the regulation of Cyp7a1, fecal bile acid concentration, or fecal energy loss.

Competition history

• JSHS 2024 Category not listed

Resources

• National JSHS abstract book ↗

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