Activation of Nrf2 decreases bile acid concentrations in livers of female mice.
Level 5 - mechanism / opinion, no new human data
Preclinical animal model study (non-human data)
PubMed 33522359 · doi:10.1080/00498254.2021.1880033
What was done
Researchers investigated the effects of Nrf2 activation on bile acid homeostasis in female mice using two approaches: pharmacological activation with CDDO-imidazolide (CDDO-Im) and genetic modulation of Keap1. The study measured hepatic and ileal mRNA levels of Nrf2 target genes (Mrp2, Mrp3), liver bile acid concentrations, biliary bile acid excretion, ileal bile acid absorption, and regulatory pathway markers including ileal Fxr-Fgf15 signalling and hepatic Cyp7a1 mRNA expression.
What was found
Both pharmacological and genetic Nrf2 activation increased hepatic and ileal mRNA levels of Mrp2 and Mrp3 and decreased liver bile acid concentrations. The lower bile acid levels were not accompanied by increased biliary excretion or decreased ileal absorption, but coincided with downregulation of hepatic Cyp7a1 mRNA and upregulation of ileal Fxr-Fgf15 signalling. The abstract reports no numerical values, effect sizes, or variance.
Why it matters
These findings suggest that Nrf2 activation lowers hepatic bile acid levels in female mice primarily by suppressing synthesis via the Fxr-Fgf15 axis, expanding on previous work limited to male rodents.
Limits
The study is restricted to a mouse model, precluding direct clinical translation to humans. The abstract does not disclose sample sizes, treatment duration, drug dosages, or quantitative outcome data.
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