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Pathway Preferential Estrogens Prevent Hepatosteatosis Due to Ovariectomy and High-Fat Diets

About 20–30% of premenopausal women have metabolic syndrome, and the number is almost double in postmenopausal women, and these women have an increased risk of hepatosteatosis. Postmenopausal women with metabolic syndrome are often treated with hormone replacement therapy (HRT), but estrogens in cur...

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Autores principales: Zuo, Qianying, Chen, Karen L., Arredondo Eve, Alicia, Liu, Yu-Jeh, Kim, Sung Hoon, Katzenellenbogen, Benita S., Katzenellenbogen, John A., Madak-Erdogan, Zeynep
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8540756/
https://www.ncbi.nlm.nih.gov/pubmed/34684335
http://dx.doi.org/10.3390/nu13103334
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author Zuo, Qianying
Chen, Karen L.
Arredondo Eve, Alicia
Liu, Yu-Jeh
Kim, Sung Hoon
Katzenellenbogen, Benita S.
Katzenellenbogen, John A.
Madak-Erdogan, Zeynep
author_facet Zuo, Qianying
Chen, Karen L.
Arredondo Eve, Alicia
Liu, Yu-Jeh
Kim, Sung Hoon
Katzenellenbogen, Benita S.
Katzenellenbogen, John A.
Madak-Erdogan, Zeynep
author_sort Zuo, Qianying
collection PubMed
description About 20–30% of premenopausal women have metabolic syndrome, and the number is almost double in postmenopausal women, and these women have an increased risk of hepatosteatosis. Postmenopausal women with metabolic syndrome are often treated with hormone replacement therapy (HRT), but estrogens in currently available HRTs increase the risk of breast and endometrial cancers and Cardiovascular Disease. Therefore, there is a critical need to find safer alternatives to HRT to improve postmenopausal metabolic health. Pathway preferential estrogen 1 (PaPE-1) is a novel estrogen receptor ligand that has been shown to favorably affect metabolic tissues without adverse effects on reproductive tissues. In this study, we have examined the effects of PaPE-1 on metabolic health, in particular, examining its effects on the liver transcriptome and on plasma metabolites in two different mouse models: diet-induced obesity (DIO) and leptin-deficient (ob/ob) mice. PaPE-1 significantly decreased liver weight and lipid accumulation in both DIO and ob/ob models and lowered the expression of genes associated with fatty acid metabolism and collagen deposition. In addition, PaPE-1 significantly increased the expression of mitochondrial genes, particularly ones associated with the electron transport chain, suggesting an increase in energy expenditure. Integrated pathway analysis using transcriptomics and metabolomics data showed that PaPE-1 treatment lowered inflammation, collagen deposition, and pathways regulating fatty acid metabolism and increased metabolites associated with glutathione metabolism. Overall, our findings support a beneficial metabolic role for PaPE-1 and suggest that PaPE-1 may protect postmenopausal women from fatty liver disease without increasing reproductive cancer risk.
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spelling pubmed-85407562021-10-24 Pathway Preferential Estrogens Prevent Hepatosteatosis Due to Ovariectomy and High-Fat Diets Zuo, Qianying Chen, Karen L. Arredondo Eve, Alicia Liu, Yu-Jeh Kim, Sung Hoon Katzenellenbogen, Benita S. Katzenellenbogen, John A. Madak-Erdogan, Zeynep Nutrients Article About 20–30% of premenopausal women have metabolic syndrome, and the number is almost double in postmenopausal women, and these women have an increased risk of hepatosteatosis. Postmenopausal women with metabolic syndrome are often treated with hormone replacement therapy (HRT), but estrogens in currently available HRTs increase the risk of breast and endometrial cancers and Cardiovascular Disease. Therefore, there is a critical need to find safer alternatives to HRT to improve postmenopausal metabolic health. Pathway preferential estrogen 1 (PaPE-1) is a novel estrogen receptor ligand that has been shown to favorably affect metabolic tissues without adverse effects on reproductive tissues. In this study, we have examined the effects of PaPE-1 on metabolic health, in particular, examining its effects on the liver transcriptome and on plasma metabolites in two different mouse models: diet-induced obesity (DIO) and leptin-deficient (ob/ob) mice. PaPE-1 significantly decreased liver weight and lipid accumulation in both DIO and ob/ob models and lowered the expression of genes associated with fatty acid metabolism and collagen deposition. In addition, PaPE-1 significantly increased the expression of mitochondrial genes, particularly ones associated with the electron transport chain, suggesting an increase in energy expenditure. Integrated pathway analysis using transcriptomics and metabolomics data showed that PaPE-1 treatment lowered inflammation, collagen deposition, and pathways regulating fatty acid metabolism and increased metabolites associated with glutathione metabolism. Overall, our findings support a beneficial metabolic role for PaPE-1 and suggest that PaPE-1 may protect postmenopausal women from fatty liver disease without increasing reproductive cancer risk. MDPI 2021-09-23 /pmc/articles/PMC8540756/ /pubmed/34684335 http://dx.doi.org/10.3390/nu13103334 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zuo, Qianying
Chen, Karen L.
Arredondo Eve, Alicia
Liu, Yu-Jeh
Kim, Sung Hoon
Katzenellenbogen, Benita S.
Katzenellenbogen, John A.
Madak-Erdogan, Zeynep
Pathway Preferential Estrogens Prevent Hepatosteatosis Due to Ovariectomy and High-Fat Diets
title Pathway Preferential Estrogens Prevent Hepatosteatosis Due to Ovariectomy and High-Fat Diets
title_full Pathway Preferential Estrogens Prevent Hepatosteatosis Due to Ovariectomy and High-Fat Diets
title_fullStr Pathway Preferential Estrogens Prevent Hepatosteatosis Due to Ovariectomy and High-Fat Diets
title_full_unstemmed Pathway Preferential Estrogens Prevent Hepatosteatosis Due to Ovariectomy and High-Fat Diets
title_short Pathway Preferential Estrogens Prevent Hepatosteatosis Due to Ovariectomy and High-Fat Diets
title_sort pathway preferential estrogens prevent hepatosteatosis due to ovariectomy and high-fat diets
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8540756/
https://www.ncbi.nlm.nih.gov/pubmed/34684335
http://dx.doi.org/10.3390/nu13103334
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