| Rhein ameliorates fatty liver disease through negative energy balance, hepatic lipogenic regulation and immunomodulation in diet-induced obese mice. | |
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MedLine Citation:
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PMID: 21364120 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Non-alcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance and inflammatory disorders. In this study, we tested the effect of rhein, a lipophilic anthraquinone derived from a traditional Chinese herbal medicine rheum palmatum L., on NAFLD-associated hepatic steatosis, insulin resistance and the Th1/Th2 cytokine imbalance in high-fat diet-induced obese (DIO) mice. We found that oral administration of rhein for 40 days significantly increased energy expenditure, reduced body weight, particularly body fat content, improved insulin resistance, lowered circulating cholesterol levels in DIO mice without affecting food intake. Rhein treatment also reduced liver triglyceride levels, reversed hepatic steatosis and normalized alanine aminotransferase (ALT) levels in these mice. Gene analysis and western blot showed that rhein markedly suppressed the expression of lipogenic enzyme sterol regulatory element-binding protein 1c (SREBP-1c) and its target genes in the liver. Luciferase reporter assay revealed that rhein suppressed the transcriptional activity of SREBP-1c through its upstream regulator, liver X receptor (LXR). This suggests that rhein exerts its effects by targeting LXR, which is also supported by its inability to reduce body weight in LXR-knockout mice. Moreover, multiplex ELISA displayed a down-regulated T helper (Th) 1 response after rhein treatment. Rhein shifted the Th1/Th2 responses by inhibiting T-box expressed in T-cells (T-bet) expression and enhancing GATA-binding protein-3 (GATA-3) expression through increased signal transducers and activators of transcription 6 (STAT6) phosphorylation. These data indicate that rhein ameliorated non-alcoholic fatty liver disease and associated disorders through LXR-mediated negative energy balance, metabolic regulatory pathways and immunomodulatory activities involved in hepatic steatosis. The combined effects of rhein to target hepatic metabolic and immune pathways may be beneficial for complex metabolic diseases such as NAFLD. |
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Authors:
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Xiaoyan Sheng; Ming Wang; Meng Lu; Beili Xi; Hongguang Sheng; Ying Qin Zang |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-3-1 |
Journal Detail:
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Title: American journal of physiology. Endocrinology and metabolism Volume: - ISSN: 1522-1555 ISO Abbreviation: - Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-3-2 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901226 Medline TA: Am J Physiol Endocrinol Metab Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1Shanghai Institutes for Biological Sciences. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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