The Role of Tanshinone IIA in the Treatment of Obesity through Peroxisome Proliferator-Activated Receptor γ Antagonism
The Role of Tanshinone IIA in the Treatment of Obesity through Peroxisome Proliferator-Activated Receptor γ Antagonism
复制标题
DOI：
10.1210/en.2008-0322
复制
发表时间：
2009-01-01
期刊：
影响因子：
4.8
通讯作者：
Zang, Ying Qin
中科院分区：
文献类型：
--
作者：
Gong, Zhenwei;Huang, Cheng;Zang, Ying Qin
过氧化物酶体增殖物激活受体 (PPAR) γ 是一种协调碳水化合物和脂质代谢的核受体，是 2 型糖尿病的治疗靶点。丹参酮IIA（Tan）是一种亲脂性二萜，在中药中广泛用于治疗心血管疾病，最近发现其具有减轻体重和降低血脂的作用。然而，其抗脂肪形成作用的潜在机制仍不清楚。在这里，我们报告 Tan 抑制 3T3-L1 前脂肪细胞分化和全长 PPAR γ 和 PPAR γ 配体结合域的转录活性。 Tan 的作用是通过其作为 PPAR γ 天然拮抗剂的特性来介导的（抑制剂值的解离常数，2.562 +/- 0.711 mu M）。 Tan治疗减少了脂肪量和体重，改善了葡萄糖耐量，并降低了低密度脂蛋白与高密度脂蛋白的比率，而不改变高脂肪饮食诱导的肥胖动物模型的食物摄入量。我们的结果表明，Tan 在脂肪生成、葡萄糖耐量、脂肪生成和心血管保护方面的综合特性有利于治疗具有复杂代谢状况的糖尿病患者，在这些患者中，调节单一靶点通常不足以达到预期效果。 （内分泌学 150：104-113，2009）
Peroxisome proliferator-activated receptor (PPAR) gamma is a nuclear receptor that coordinates carbohydrate and lipid metabolism, and is a therapeutic target for type 2 diabetes. Tanshinone IIA ( Tan) is a lipophilic diterpene that is widely used to treat cardiovascular diseases in traditional Chinese medicine, and has recently been found to reduce body weight and lower blood lipids. However, its underlying mechanism of antiadipogenic effects remains unknown. Here, we report that Tan inhibits 3T3-L1 preadipocyte differentiation and transcriptional activities of full-length PPAR gamma and PPAR gamma ligand-binding domains. The effects of Tan are mediated through its property as a natural antagonist of PPAR gamma (dissociation constant of an inhibitor value, 2.562 +/- 0.711 mu M). Tan treatment reduced adipose mass and body weight, improved glucose tolerance, and lowered the low-density lipoprotein to high-density lipoprotein ratio without changing the food intake in a high-fat diet-induced obese animal model. Our results suggest that the combined properties of Tan in adipogenesis, glucose tolerance, lipogenesis, and cardiovascular protection are beneficial for treating diabetic patients with complex metabolic conditions, in which modulating a single target is often not sufficient to achieve the desired effect. (Endocrinology 150: 104-113, 2009)