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

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

Author information

1
Division of Nutritional Sciences, UIUC, Urbana, Illinois, United States of America.
2
Department of Food Science and Human Nutrition, UIUC, Urbana, Illinois, United States of America.
3
Institute for Genomic Biology, UIUC, Urbana, Illinois, United States of America.
4
National Center for Supercomputing Applications, UIUC, Urbana, Illinois, United States of America.

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.

PMID:
29267318
PMCID:
PMC5739449
DOI:
10.1371/journal.pone.0189911
[Indexed for MEDLINE]
Free PMC Article

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