Rheum palmatum has been used most frequently in the weight-reducing formulae in traditional Chinese medicine. However, the components of Rheum palmatum that play the antiobesity role are still uncertain. Here, we tested the weight-reducing effect of two major Rheum palmatum compounds on mouse. We found that rhein (100？mg kg？1？day？1), but not emodin, reduced the fat weight in mouse. Using diet-induced obese (DIO) C57BL/6 mice, we identified that rhein blocked high-fat diet-induced obesity, decreased fat mass and the size of white and brown adipocytes, and lowered serum cholesterol, LDL cholesterol, and fasting blood glucose levels in the mice. To elucidate the underlying mechanisms, we used reporter assay and gene expression analysis and found that rhein inhibited peroxisome proliferator-activated receptor γ (PPARγ) transactivity and the expression of its target genes, suggesting that rhein may act as a PPARγ antagonist. Our data indicate that rhein may be a promising choice for antiobesity therapy. 1. Introduction Obesity is one of the most serious public health problems of the 21st century [1, 2]. It increases the risk of various fetal diseases, particularly coronary artery disease, type II diabetes, hypertension, dyslipidemia, and certain types of cancer [3–5]. At present, there is only one drug, orlistat, approved by the Food and Drug Administration (FDA) for long-term use in the treatment of obesity. Thus, it is urgent to develop a new therapy for the prevention and treatment of obesity [5]. The development of novel antiobesity drugs has been proven difficult because of side-effects and lower efficiency [6–9]. Traditional medicine has various herbs for weight-reducing practice and may be a potential source for novel antiobesity drugs. Rheum palmatum is used most frequently in the weight-reducing formulae of traditional Chinese medicine. Recently, rhein, one of the major components of Rheum palmatum, has been shown to be an inhibitor of 3T3-L1 adipocyte differentiation [10]. Moreover, rhein has been reported to have pharmacological and biochemical effects on the inhibition of liver fibrosis and insulin sensitizing [11–13] and prevent hepatic steatosis through LXR inhibition in a high-fat diet-induced obese mouse model [14]. However, whether rhein plays the antiobesity role in vivo is still uncertain and the underlying mechanisms also need to be elucidated. In the present study, we compared the weight-reducing effect of two major compounds from Rheum palmatum. We found that rhein reduced fat weight in mouse. We also showed that rhein blocked weight
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