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Our recent study suggested that gastrointestinal tract and liver were important targets mediating the anti-obesity effects of intragastric safflower yellow (SY). Therefore, our present study aims to investigate the effect of intragastric SY on MAFLD and possible mechanism. DIO mice were treated with 125 mg\/kg\/d SY for 12 weeks by gavage. We found intragastric SY significantly slowed weight gain of body, reduced the food intake and liver weight, improved hepatic steatosis, liver function and glucose metabolism in DIO mice. The comparison between OGTT and IPGTT illustrated OGTT produced a better improvement of glucose tolerance after SY treatment. We also found intragastric SY significantly increased the energy expenditure and locomotor activity of DIO mice. SY obviously decreased the expression of lipogenesis-associated and ERS-related genes in liver of DIO mice and PA-induced MAFLD hepatocyte model. Gut microbiota analysis demonstrated intragastric SY apparently changed the diversity and composition of gut microbiota of DIO mice. Further function prediction analysis indicated that gut microbiotas in SY-treated mice was positively related with energy metabolism, lipid metabolism and endocrine system. Intragastric SY has a significant therapeutic effect on MAFLD, which is mediated partly by modulating gut microbiota and improving liver ERS.<\/jats:p>","DOI":"10.3390\/nu15132954","type":"journal-article","created":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T01:02:41Z","timestamp":1688086961000},"page":"2954","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Intragastric Safflower Yellow Alleviates HFD Induced Metabolic Dysfunction-Associated Fatty Liver Disease in Mice through Regulating Gut Microbiota and Liver Endoplasmic Reticulum Stress"],"prefix":"10.3390","volume":"15","author":[{"given":"Wenjing","family":"Hu","sequence":"first","affiliation":[{"name":"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, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaorui","family":"Lyu","sequence":"additional","affiliation":[{"name":"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, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7209-5166","authenticated-orcid":false,"given":"Hanyuan","family":"Xu","sequence":"additional","affiliation":[{"name":"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, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaonan","family":"Guo","sequence":"additional","affiliation":[{"name":"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, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huijuan","family":"Zhu","sequence":"additional","affiliation":[{"name":"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, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2413-0646","authenticated-orcid":false,"given":"Hui","family":"Pan","sequence":"additional","affiliation":[{"name":"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, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linjie","family":"Wang","sequence":"additional","affiliation":[{"name":"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, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongbo","family":"Yang","sequence":"additional","affiliation":[{"name":"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, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fengying","family":"Gong","sequence":"additional","affiliation":[{"name":"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, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1053\/j.gastro.2019.11.312","article-title":"MAFLD: A Consensus-Driven Proposed Nomenclature for Metabolic Associated Fatty Liver Disease","volume":"158","author":"Eslam","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.jhep.2020.03.039","article-title":"A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement","volume":"73","author":"Eslam","year":"2020","journal-title":"J. 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