Safflower yellow and its main component hydroxysafflor yellow A alleviate hyperleptinemia in diet-induced obesity mice through a dual inhibition of the GIP-GIPR signaling axis.

IF 6.1 2区 医学 Q1 CHEMISTRY, MEDICINAL Phytotherapy Research Pub Date : 2024-10-01 Epub Date: 2023-03-21 DOI:10.1002/ptr.7788
Xiaorui Lyu, Kemin Yan, WenJing Hu, Hanyuan Xu, Xiaonan Guo, Zhibo Zhou, Huijuan Zhu, Hui Pan, Linjie Wang, Hongbo Yang, Fengying Gong
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Abstract

Glucose-dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone secreted by K cells in the small intestine and is considered an obesity-promoting factor. In this study, we systematically investigated the anti-obesity effects of intragastric safflower yellow (SY)/hydroxysafflor yellow A (HSYA) and the underlying mechanism for the first time. Our results showed that intragastric SY/HSYA, rather than an intraperitoneal injection, notably decreased serum GIP levels and GIP staining in the small intestine in diet-induced obese (DIO) mice. Moreover, intragastric SY/HSYA was also first found to significantly suppress GIP receptor (GIPR) signaling in both the hypothalamus and subcutaneous White adipose tissue. Our study is the first to show that intragastric SY/HSYA obviously reduced food intake and body weight gain in leptin sensitivity experiments and decreased serum leptin levels in DIO mice. Further experiments demonstrated that SY treatment also significantly reduced leptin levels, whereas the inhibitory effect of SY on leptin levels was reversed by activating GIPR in 3 T3-L1 adipocytes. In addition, intragastric SY/HSYA had already significantly reduced serum GIP levels and GIPR expression before the serum leptin levels were notably changed in high-fat-diet-fed mice. These findings suggested that intragastric SY/HSYA may alleviate diet-induced obesity in mice by ameliorating hyperleptinemia via dual inhibition of the GIP-GIPR axis.

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红花黄色素及其主要成分羟基红花黄色素 A 可通过对 GIP-GIPR 信号轴的双重抑制,缓解饮食诱导肥胖小鼠的高瘦素血症。
葡萄糖依赖性促胰岛素多肽(GIP)是一种由小肠K细胞分泌的胃肠道激素,被认为是一种肥胖促进因素。在这项研究中,我们首次系统地研究了胃内红花黄色素(SY)/羟基红花黄色素A(HSYA)的抗肥胖作用及其内在机制。我们的研究结果表明,与腹腔注射相比,胃内注射 SY/HSYA 能显著降低饮食诱导肥胖(DIO)小鼠的血清 GIP 水平和小肠中的 GIP 染色。此外,首次发现胃内注射 SY/HSYA 还能显著抑制下丘脑和皮下白色脂肪组织中的 GIP 受体(GIPR)信号传导。我们的研究首次表明,在瘦素敏感性实验中,胃内SY/HSYA可明显减少小鼠的食物摄入量和体重增加,并降低DIO小鼠的血清瘦素水平。进一步的实验表明,SY 处理也会显著降低瘦素水平,而通过激活 3 T3-L1 脂肪细胞中的 GIPR 可以逆转 SY 对瘦素水平的抑制作用。此外,在高脂饮食喂养的小鼠血清瘦素水平发生明显变化之前,胃内 SY/HSYA 已经显著降低了血清 GIP 水平和 GIPR 表达。这些研究结果表明,胃内 SY/HSYA 可通过对 GIP-GIPR 轴的双重抑制,改善高瘦素血症,从而缓解饮食引起的小鼠肥胖。
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来源期刊
Phytotherapy Research
Phytotherapy Research 医学-药学
CiteScore
12.80
自引率
5.60%
发文量
325
审稿时长
2.6 months
期刊介绍: Phytotherapy Research is an internationally recognized pharmacological journal that serves as a trailblazing resource for biochemists, pharmacologists, and toxicologists. We strive to disseminate groundbreaking research on medicinal plants, pushing the boundaries of knowledge and understanding in this field. Our primary focus areas encompass pharmacology, toxicology, and the clinical applications of herbs and natural products in medicine. We actively encourage submissions on the effects of commonly consumed food ingredients and standardized plant extracts. We welcome a range of contributions including original research papers, review articles, and letters. By providing a platform for the latest developments and discoveries in phytotherapy, we aim to support the advancement of scientific knowledge and contribute to the improvement of modern medicine.
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