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International Journal Of Bilogical Sciences

.: Home > International Journal Of Bilogical Sciences > 2012 > Volume 8 Number 10 > Xiaoyan Sheng1,*, Xuehua Zhu2,*, Yuebo Zhang1, Guoliang Cui1, Linling Peng3, Xiong Lu4, Ying Qin Zang1,✉

Rhein Protects against Obesity and Related Metabolic Disorders through Liver X Receptor-Mediated Uncoupling Protein 1 Upregulation in Brown Adipose Tissue

Xiaoyan Sheng1,*, Xuehua Zhu2,*, Yuebo Zhang1, Guoliang Cui1, Linling Peng3, Xiong Lu4, Ying Qin Zang1,✉
1. Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of CAS, Chinese Academy of Sciences, Shanghai 200031, China 2. Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, China 3. State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China 4. Laboratory of Cell Biology and Histopathology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
Abstract :

Liver X receptors (LXRs) play important roles in regulating cholesterol homeostasis, and lipid and energy metabolism. Therefore, LXR ligands could be used for the management of metabolic disorders. We evaluated rhein, a natural compound from Rheum palmatum L., as an antagonist for LXRs and investigated its anti-obesity mechanism in high-fat diet-fed mice. Surface plasmon resonance assays were performed to examine the direct binding of rhein to LXRs. LXR target gene expression was assessed in 3T3-L1 adipocytes and HepG2 hepatic cells in vitro. C57BL/6J mice fed a high-fat diet were orally administered with rhein for 4 weeks, and then the expression levels of LXR-related genes were analyzed. Rhein bound directly to LXRs. The expression levels of LXR target genes were suppressed by rhein in 3T3-L1 and HepG2 cells. In white adipose tissue, muscle and liver, rhein reprogrammed the expression of LXR target genes related to adipogenesis and cholesterol metabolism. Rhein activated uncoupling protein 1 (UCP1) expression in brown adipose tissue (BAT) in wild-type mice, but did not affect UCP1 expression in LXR knockout mice. In HIB-1B brown adipocytes, rhein activated the UCP1 gene by antagonizing the repressive effect of LXR on UCP1 expression. This study suggests that rhein may protect against obesity and related metabolic disorders through LXR antagonism and regulation of UCP1 expression in BAT.

Keywords :
LXR, diet-induced obesity, UCP1, antagonist, rhein.

Date Deposited : 09 Apr 2015 14:51

Last Modified : 09 Apr 2015 14:51

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Volume 8, Number 10, - 2012 , ISSN 1545-1003

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