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

11 Citations (Scopus)

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

Fingerprint

Liver Regeneration
Microbiota
Tretinoin
Bile Acids and Salts
Liver
Bacteroidetes
Hepatocytes
Homeostasis
Biological Phenomena
Lipids
AMP-Activated Protein Kinases
Hepatectomy
Inbred C57BL Mouse
Cell Proliferation

Keywords

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

ASJC Scopus subject areas

  • Oncology

Cite this

Microbiota and bile acid profiles in retinoic acid-primed mice that exhibit accelerated liver regeneration. / Liu, Hui Xin; Hu, Ying; Wan, Yu-Jui Yvonne.

In: Oncotarget, Vol. 7, No. 2, 2016, p. 1096-1106.

Research output: Contribution to journalArticle

@article{434e6ebdab10448c81a1b4ea7700e228,
title = "Microbiota and bile acid profiles in retinoic acid-primed mice that exhibit accelerated liver regeneration",
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.",
keywords = "Energy metabolism, Fibroblast growth factor 21, Gut-liver axis, Lipid homeostasis, Partial hepatectomy, Pathology Section",
author = "Liu, {Hui Xin} and Ying Hu and Wan, {Yu-Jui Yvonne}",
year = "2016",
doi = "10.18632/oncotarget.6665",
language = "English (US)",
volume = "7",
pages = "1096--1106",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "2",

}

TY - JOUR

T1 - Microbiota and bile acid profiles in retinoic acid-primed mice that exhibit accelerated liver regeneration

AU - Liu, Hui Xin

AU - Hu, Ying

AU - Wan, Yu-Jui Yvonne

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

KW - Energy metabolism

KW - Fibroblast growth factor 21

KW - Gut-liver axis

KW - Lipid homeostasis

KW - Partial hepatectomy

KW - Pathology Section

UR - http://www.scopus.com/inward/record.url?scp=84957695751&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84957695751&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.6665

DO - 10.18632/oncotarget.6665

M3 - Article

VL - 7

SP - 1096

EP - 1106

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 2

ER -