Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, 1# Shuaifuyuan, Wangfujing, , 100730, Beijing, China.
Naunyn Schmiedebergs Arch Pharmacol. 2022 May;395(5):579-591. doi: 10.1007/s00210-022-02220-8. Epub 2022 Feb 24.
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.
我们之前的研究发现，红花黄色素（SY）及其主要成分羟基红花黄色素 A（HSYA）可减轻高脂饮食（HFD）诱导肥胖小鼠的肥胖并改善瘦素抵抗。因此，本研究旨在探讨 SY/HSYA 的上述作用是减肥的直接作用还是后续作用，以及瘦素是否是 SY/HSYA 抗肥胖作用所必需的。用 SY 或 HSYA 处理 HFD 诱导肥胖的小鼠 4 周，用 SY 处理 ob/ob 小鼠 10 周。测量体重、食物摄入量、脂肪量和血清瘦素水平。在 HFD 诱导肥胖的小鼠中进行瘦素敏感性实验。通过 RT-qPCR 和 Western blot 方法检测瘦素及其信号相关基因的表达。SY/HSYA 处理对 HFD 诱导肥胖小鼠的食物摄入量、能量消耗、体重、脂肪量和血清瘦素水平没有影响。然而，瘦素敏感性实验显示，HFD-SY 组的食物摄入量减少了 18.4%，HFD-HSYA 组的体重增加减少了 104.6%（均 P<0.05）。此外，HFD 诱导肥胖小鼠的白色脂肪组织中瘦素及其信号抑制调节因子的表达显著降低，而信号转导和转录激活因子 3（p-STAT3）的磷酸化明显增加，完全分化的 3T3-L1 脂肪细胞经 SY/HSYA 干预后（均 P<0.05）。有趣的是，SY 处理对瘦素缺乏型 ob/ob 小鼠的体重、脂肪量和葡萄糖代谢没有影响。SY/HSYA 给药可首先改善 HFD 诱导肥胖小鼠脂肪组织的外周瘦素抵抗，而瘦素是 SY 抗肥胖作用所必需的。
