Pathway Preferential Estrogens Prevent Hepatosteatosis Due to Ovariectomy and High-Fat Diets
| Autor: | Sung Hoon Kim, John A. Katzenellenbogen, Benita S. Katzenellenbogen, Karen L. Chen, Alicia Arredondo Eve, Qianying Zuo, Yu Jeh Liu, Zeynep Madak-Erdogan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_treatment
Estrogen receptor Mice Obese Ligands Weight Gain Transcriptome chemistry.chemical_compound hepatosteatosis TX341-641 Nutrition and Dietetics Fatty liver Hormone replacement therapy (menopause) Hep G2 Cells Organ Size high-fat diet Liver pathway preferential estrogen 1 (PaPE-1) Collagen non-alcoholic fatty liver disease (NAFLD) medicine.medical_specialty medicine.drug_class Ovariectomy Diet High-Fat Article Internal medicine medicine Animals Humans Metabolomics Obesity Inflammation metabolic health Fatty acid metabolism business.industry Nutrition. Foods and food supply Body Weight Estrogen Receptor alpha Estrogens medicine.disease Lipid Metabolism Fatty Liver Mice Inbred C57BL Endocrinology chemistry Estrogen Hepatocytes Metabolic syndrome business Food Science |
| Zdroj: | Nutrients Volume 13 Issue 10 Nutrients, Vol 13, Iss 3334, p 3334 (2021) |
| ISSN: | 2072-6643 |
| DOI: | 10.3390/nu13103334 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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