Safflower yellow improves insulin sensitivity in high-fat diet-induced obese mice by promoting peroxisome proliferator-activated receptor-γ2 expression in subcutaneous adipose tissue

Abstract

Aims/Introduction: Safflower yellow (SY) and its main component, hydroxysafflor yellow A, have been demonstrated to show anti-obesity effects. Peroxisome proliferator-activated receptor-γ2 (PPARγ2) is a critical transcription factor in adipose tissue metabolism. The aim of the present study was to explore the effects of SY in high-fat diet-induced obese mice, and further investigate the mechanism involving PPARγ2. Methods: High-fat diet-induced obese mice were given 120 mg/kg/day SY for 8 weeks. Glucose and insulin tolerance tests were carried out. 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 was measured. In vitro, the effects of SY (0–500 mg/L) and hydroxysafflor yellow A (0–100 mg/L) on PPARγ2 promoter activities and PPARγ2 messenger ribonucleic acid (mRNA) levels in 3T3-L1 preadipocytes or adipocytes were also detected. Results: Safflower yellow 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 hydroxysafflor yellow A significantly enhanced PPARγ2 promoter activities by 1.3–2.1-fold, and increased PPARγ2 mRNA levels by 1.2–1.6-fold in 3T3-L1 preadipocytes or adipocytes (P < 0.05). Conclusions: SY could reduce fat mass, decrease glucose levels and improve insulin sensitivity in high-fat diet-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.