The Hexane Fraction ofCyperus rotundusPrevents Non-Alcoholic Fatty Liver Disease Through the Inhibition of Liver X Receptor α-Mediated Activation of Sterol Regulatory Element Binding Protein-1c
| Autor: | Jong Hwan Kwak, Jin Yoon, Seung-Whan Kim, Gang Gu Lee, Gyun-Sik Oh |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_specialty
Transcription Genetic Response element RNA polymerase II Biology Non-alcoholic Fatty Liver Disease Transcription (biology) Internal medicine medicine Animals Hexanes Cyperus Promoter Regions Genetic Liver X receptor Cells Cultured Triglycerides Liver X Receptors Plant Extracts Lipogenesis Reverse cholesterol transport Fatty liver General Medicine Orphan Nuclear Receptors medicine.disease Sterol Mice Inbred C57BL Endocrinology Complementary and alternative medicine Hepatocytes biology.protein RNA Polymerase II Sterol Regulatory Element Binding Protein 1 Phytotherapy |
| Zdroj: | The American Journal of Chinese Medicine. 43:477-494 |
| ISSN: | 1793-6853 0192-415X |
| DOI: | 10.1142/s0192415x15500305 |
| Popis: | The goals of this study were (1) to examine the effects of Cyperus rotundus (CR) rhizome on cellular lipogenesis and non-alcoholic/diet-induced fatty liver disease, and (2) to elucidate the molecular mechanism behind its actions. The present investigation showed that the hexane fraction of CR rhizome (CRHF) reduced the elevated transcription levels of sterol regulatory element binding protein-1c (SREBP-1c) in primary hepatocytes following exposure to the liver X receptor α (LXRα) agonist. The SREBP-1c gene is a master regulator of lipogenesis and a key target of LXRα. CRHF inhibited not only the LXRα-dependent activation of the synthetic LXR response element (LXRE) promoter, but also the activation of the natural SREBP-1c promoter. Moreover, CRHF decreased (a) the recruitment of RNA polymerase II to the LXRE of the SREBP-1c gene; (b) the LXRα-dependent up-regulation of various lipogenic genes; and (c) the LXRα-mediated accumulation of triglycerides in primary hepatocytes. Furthermore, CRHF ameliorated fatty liver disease and reduced the expression levels of hepatic lipogenic genes in high sucrose diet (HSD)-fed mice. Interestingly, CRHF did not affect the expression of ATP-binding cassette transporter A1, another important LXR target gene that is required for reverse cholesterol transport (RCT) and protects against atherosclerosis. Taken together, these results suggest that CRHF might be a novel therapeutic remedy for fatty liver disease through the selective inhibition of the lipogenic pathway. |
| Databáze: | OpenAIRE |
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