Microbiota and bile acid profiles in retinoic acid-primed mice that exhibit accelerated liver regeneration

Hui Xin Liu, Ying Hu, Yu-Jui Yvonne Wan

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Background & Aims: All-trans Retinoic acid (RA) regulates hepatic lipid and bile acid homeostasis. Similar to bile acid (BA), RA accelerates partial hepatectomy (PHx)- induced liver regeneration. Because there is a bidirectional regulatory relationship between gut microbiota and BA synthesis, we examined the effect of RA in altering the gut microbial population and BA composition and established their relationship with hepatic biological processes during the active phases of liver regeneration. Methods: C57BL/6 mice were treated with RA orally followed by 2/3 PHx. The roles of RA in shifting gut microbiota and BA profiles as well as hepatocyte metabolism and proliferation were studied. Results: RA-primed mice exhibited accelerated hepatocyte proliferation revealed by higher numbers of Ki67-positive cells compared to untreated mice. Firmicutes and Bacteroidetes phyla dominated the gut microbial community (> 85%) in both control and RA-primed mice after PHx. RA reduced the ratio of Firmicutes to Bacteroidetes, which was associated with a lean phenotype. Consistently, RA-primed mice lacked transient lipid accumulation normally found in regenerating livers. In addition, RA altered BA homeostasis and shifted BA profiles by increasing the ratio of hydrophilic to hydrophobic BAs in regenerating livers. Accordingly, metabolic regulators fibroblast growth factor 21, Sirtuin1, and their downstream targets AMPK and ERK1/2 were more robustly activated in RA-primed than unprimed regenerating livers. Conclusions: Priming mice with RA resulted in a lean microbiota composition and hydrophilic BA profiles, which were associated with facilitated metabolism and enhanced cell proliferation.

Original languageEnglish (US)
Pages (from-to)1096-1106
Number of pages11
JournalOncotarget
Volume7
Issue number2
DOIs
StatePublished - 2016

Keywords

  • Energy metabolism
  • Fibroblast growth factor 21
  • Gut-liver axis
  • Lipid homeostasis
  • Partial hepatectomy
  • Pathology Section

ASJC Scopus subject areas

  • Oncology

Fingerprint Dive into the research topics of 'Microbiota and bile acid profiles in retinoic acid-primed mice that exhibit accelerated liver regeneration'. Together they form a unique fingerprint.

  • Cite this