Bazedoxifene and conjugated estrogen combination maintains metabolic homeostasis and benefits liver health

PLoS One. 2017 Dec 21;12(12):e0189911. doi: 10.1371/journal.pone.0189911. eCollection 2017.

Abstract

The bazedoxifene and conjugated estrogens (CE+BZA) combination has been shown to prevent visceral adiposity and weight gain after ovariectomy. However, its impact on the liver transcriptomes associated with prevention of hepatosteatosis is yet to be determined. In the present study, we use liver transcriptomics and plasma metabolomics analysis to characterize the effects of various estrogens on liver. The CE+BZA combination was very effective at preventing ovariectomy-induced weight gain in mice fed a high-fat diet (HFD). In CE+BZA treated animals, liver weight and hepatic lipid deposition were significantly lower than in Vehicle (Veh) treated animals. Additionally, CE+BZA induced unique liver transcriptome and plasma metabolome profiles compared to estradiol, conjugated estrogens alone, and bazedoxifene alone. Blood plasma metabolite analysis identified several metabolites similar to and distinct from other estrogen treatments. Integrated pathway analysis showed that gene networks that were associated with inflammation, reactive oxygen species pathway and lipid metabolism and their relevant metabolites were regulated significantly by CE+BZA treatment. Thus, long-term CE+BZA treatment modulated hepatic metabolic gene networks and their associated metabolites and improves hepatic health without stimulating the uterus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Estrogens, Conjugated (USP) / pharmacology*
  • Female
  • Homeostasis / drug effects*
  • Indoles / pharmacology*
  • Liver / drug effects*
  • Metabolome
  • Mice
  • Mice, Inbred C57BL
  • Ovariectomy
  • Transcriptome

Substances

  • Estrogens, Conjugated (USP)
  • Indoles
  • bazedoxifene

Grant support

This work was supported by grants from the University of Illinois, Office of the Vice Chancellor for Research, Arnold O. Beckman award RB15150 (to ZME), National Institute of Food and Agriculture, U.S. Department of Agriculture, award ILLU-698-909 (to ZME), and investigator initiated grant- WI196180 from Pfizer (to ZME). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.