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Content Provider | PubMed Central |
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Author | Zhang, Hua Liu, Yuanwu Wang, Li Zhen, Li Zhang, Hongwen Wu, Jihua Rahman, Nafis Guo, Yangdong Li, Defa Ning, Li Huhtaniemi, Ilpo Tsang, Suk Ying Gao, George F. Li, Xiangdong |
Copyright Year | 2013 |
Abstract | It is important to clarify the distinct contributions of estrogen/estrogen receptor (ER) and androgen/androgen receptor (AR) signaling and their reciprocal effects on the regulation of hepatic lipid homeostasis. We studied the molecular mechanisms underlying the preventive effects of estradiol (E2), dihydrotestosterone (DHT), or E2+DHT on high-fat diet-induced nonalcoholic fatty liver disease (NAFLD) in an orchidectomized Sprague-Dawley (SD) rat model. E2 is shown to be associated with decreased fatty acid synthesis in hepatic zone 3-specific manner by increasing the phosphorylation of acetyl coenzyme-A carboxylase via an ERα-mediated pathway. DHT is shown to be associated with decreased lipid accumulation and cholesterol synthesis in a hepatic zone 1-specific manner by increasing expression of carnitine palmitotyltransferase1 and phosphorylation of 3-hydroxy-3-methyl-glutaryl-CoA reductase via an AR-mediated pathway. E2+DHT showed an additive positive effect and normalized all three impaired zones of the liver. Gene expression changes in human severe liver steatosis were similar to those of experimental rat NAFLD. Steroids reversed the histopathological NAFLD changes, likely by decreasing fatty acid and cholesterol synthesis and increasing β-oxidation. The diverse steroid effects (ER/AR) on NAFLD prevention in male rats indicate the potential applicability of ER/AR modulators for NAFLD treatment. |
Related Links | http://dx.doi.org/10.1194/jlr.m028969 |
Ending Page | 357 |
Page Count | 13 |
Starting Page | 345 |
File Format | |
ISSN | 00222275 |
e-ISSN | 15397262 |
Journal | Journal of Lipid Research |
Issue Number | 2 |
Volume Number | 54 |
Language | English |
Publisher | The American Society for Biochemistry and Molecular Biology |
Publisher Date | 2013-02-01 |
Access Restriction | Open |
Rights Holder | The American Society for Biochemistry and Molecular Biology |
Subject Keyword | Cell Biology Biochemistry Endocrinology Research in Higher Education |
Content Type | Text |
Resource Type | Article |
Subject | Endocrinology Biochemistry Cell Biology |
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