The Role of Tanshinone IIA in the Treatment of Obesity through Peroxisome Proliferator-Activated Receptor γ Antagonism

Peroxisome proliferator-activated receptor (PPAR) γ 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 PPARγ and PPARγ ligand-binding domains. The effects of Tan are mediated through its property as a natural antagonist of PPARγ (dissociation constant of an inhibitor value, 2.562 ± 0.711 μm). 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.

Tanshinone IIA (Tan), an herbal compound, which reduces body weight and lowers blood lipids, is a natural antagonist of peroxisome proliferator-activated receptor γ.