{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:29:56Z","timestamp":1780468196389,"version":"3.54.1"},"reference-count":49,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T00:00:00Z","timestamp":1679356800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82270913"],"award-info":[{"award-number":["82270913"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Glucose\u2010dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone secreted by K cells in the small intestine and is considered an obesity\u2010promoting factor. In this study, we systematically investigated the anti\u2010obesity 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\u2010induced 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\u00a0T3\u2010L1 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\u2010fat\u2010diet\u2010fed mice. These findings suggested that intragastric SY\/HSYA may alleviate diet\u2010induced obesity in mice by ameliorating hyperleptinemia via dual inhibition of the GIP\u2010GIPR axis.<\/jats:p>","DOI":"10.1002\/ptr.7788","type":"journal-article","created":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T16:00:09Z","timestamp":1679414409000},"page":"4940-4956","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Safflower yellow and its main component hydroxysafflor yellow A alleviate hyperleptinemia in diet\u2010induced obesity mice through a dual inhibition of the GIP\u2010GIPR signaling axis"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6523-4292","authenticated-orcid":false,"given":"Xiaorui","family":"Lyu","sequence":"first","affiliation":[{"name":"Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital 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