Safflower Yellow Improves Insulin Sensitivity in High Fat Diet‐induced Obese Mice by Promoting PPARγ2 Expression in Subcutaneous Adipose Tissue

AIMS/INTRODUCTION: Safflower yellow (SY) and its main component hydroxysafflor yellow A (HSYA) have been demonstrated to show the anti-obesity effects. Peroxisome proliferative activated receptor γ2 (PPARγ2) is a critical transcription factor in adipose tissue metabolism. The aim of the study is to explore the effects of SY in high fat diet (HFD)-induced obese mice, and further investigate the mechanism involving PPARγ2. METHODS: HFD-induced obese mice were administrated with 120 mg/kg/d SY for 8 weeks. Glucose and insulin tolerance tests were conducted. Fat mass and serum levels of glucose and insulin were measured. The expression of insulin signaling pathway related genes and PPARγ2 in the adipose tissue were measured. In vitro, the effects of SY (0~500 mg/L) and HSYA (0~100 mg/L) on PPARγ2 promoter activities and PPARγ2 mRNA levels in 3T3-L1 preadipocytes or adipocytes were also detected. RESULTS: SY reduced fat mass, decreased glucose levels and improved insulin sensitivity in obese mice. SY also increased the mRNA levels of insulin signaling pathway related genes, and increased PPARγ2 mRNA levels by 39.1% in subcutaneous adipose tissue (P<0.05). In vitro, SY and HSYA significantly enhanced PPARγ2 promoter activities to 1.3~2.1 folds, and increased PPARγ2 mRNA levels to 1.2~1.6 folds in 3T3-L1 preadipocytes or adipocytes (P<0.05). CONCLUSIONS: SY could reduce fat mass, decrease glucose levels and improve insulin sensitivity in HFD-induced obese mice. The probable mechanism is to increase PPARγ2 expression by stimulating PPARγ2 promoter activities, further increasing the expression of insulin signaling pathway related genes in subcutaneous adipose tissue.