Intragastric safflower yellow and its main component HSYA improve leptin sensitivity before body weight change in diet-induced obese mice

Our previous studies found that safflower yellow (SY) and its main component hydroxysafflor yellow A (HSYA) could alleviate obesity and improve leptin resistance in high-fat diet (HFD) induced obese mice. Therefore, our present study aimed to investigate whether the above effect of SY/HSYA was a direct effect or follow-up effect of weight loss and whether leptin was essential for the anti-obesity effect of SY/HSYA or not. HFD-induced obese mice were treated with SY or HSYA for 4 weeks, while ob/ob mice were treated with SY for 10 weeks. Body weight, food intake, fat mass, and serum leptin levels were measured. The leptin sensitivity experiment was conducted in HFD-induced obese mice. The expressions of leptin and its signaling-related genes were detected by RT-qPCR and Western blot methods. SY/HSYA treatment had no effect on food intake, energy expenditure, body weight, fat mass, and serum leptin levels in HFD-induced obese mice. However, the leptin sensitivity experiment showed that the food intake decreased by 18.4% in the HFD-SY group and the body weight gain decreased by 104.6% in the HFD-HSYA group, respectively (both P < 0.05). Furthermore, the expressions of leptin and leptin signaling inhibitory regulators were significantly decreased, while the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3) were notably increased in WAT of HFD-induced obese mice, fully differentiated 3T3-L1 adipocytes after SY/HSYA intervention (all P < 0.05). Interestingly, SY treatment was ineffective on body weight, fat mass, and glucose metabolism in leptin-deficient ob/ob mice. SY/HSYA administration could firstly improve peripheral leptin resistance in adipose tissue of HFD-induced obese mice before their body weight was significantly changed, and leptin was essential for the anti-obesity effect of SY.