{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:14:25Z","timestamp":1788394465835,"version":"build-2803163510"},"reference-count":66,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T00:00:00Z","timestamp":1745539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background\/Objectives:\u00a0Xanthoceras sorbifolium oil (XSO), containing nervonic acid and unsaturated fatty acids (93%), exhibits lipid-lowering potential; yet, its mechanisms involving gut\u2013liver crosstalk remain unclear. This study investigated XSO\u2019s anti-hyperlipidemic effects and gut microbiota interactions. Methods: Forty-eight Sprague Dawley male rats were divided into: normal control (NC), high-fat diet (HFD), XSO prevention (XOP, 1.4 mL\/kg pre-HFD), and XSO treatment (XOT, post-HFD). Serum lipids, fecal short-chain fatty acids (SCFAs), gut microbiota (16S rRNA), and lipidomics (UPLC-MS\/MS) were analyzed after 12 weeks. Results: XOP significantly reduced serum total cholesterol (TC, 26.8%), triglycerides (TG, 35.9%), and low-density lipoprotein cholesterol (LDL-C, 45.9%) versus HFD (p &lt; 0.05), while increasing high-density lipoprotein cholesterol (HDL-C, 7.98%). XOP showed enhanced hepatoprotection (AST\u2193 32.6%, p &lt; 0.01). Although XSO elevated fecal acetate (1.5-fold) and butyrate (1.3-fold), these changes lacked significance (p &gt; 0.05). The analysis of gut microbiota showed that the pro-inflammatory Coriobacteriaceae and Erysipelibacteriaceae were reduced at the family level in the XOP group (p &lt; 0.05). Lipidomics identified 69 differential metabolites: XSO downregulated atherogenic cholesteryl esters and triglycerides, upregulated six phosphatidylethanolamines, and modulated aberrant lysophosphatidylcholines. Conclusions: XSO alleviates hyperlipidemia through direct modulation of lipid metabolism pathways and suppression of pro-inflammatory gut microbiota. While its prebiotic potential warrants further validation, these findings highlight XSO as a functional dietary adjunct for improving lipid homeostasis and mitigating cardiovascular risks. XSO alleviates hyperlipidemia through direct modulation of lipid metabolism pathways and suppression of pro-inflammatory gut microbiota, while its prebiotic potential warrants further validation. These findings support XSO as a dietary adjunct for lipid homeostasis improvement, offering a nutritional strategy for early-stage cardiovascular risk management.<\/jats:p>","DOI":"10.3390\/metabo15050291","type":"journal-article","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T10:42:09Z","timestamp":1745577729000},"page":"291","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Xanthoceras sorbifolium Oil Attenuates Hyperlipidemia Through Dual Modulation of Gut Microbiota and Lipid Metabolites: Mechanistic Insights from Lipidomics and 16S rRNA Sequencing"],"prefix":"10.3390","volume":"15","author":[{"given":"Yameng","family":"Tao","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences, Anhui Medical University, Hefei 230032, China"},{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaomiao","family":"Yao","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Anhui Medical University, Hefei 230032, China"},{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"He","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Anhui Medical University, Hefei 230032, China"},{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyang","family":"Kang","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"},{"name":"College of Life Sciences, Hebei University, Baoding 071002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangkai","family":"Shi","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"},{"name":"School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Hu","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"},{"name":"College of Life Sciences, Hebei University, Baoding 071002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyun","family":"Meng","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Gan","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruolan","family":"Gu","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunbo","family":"Sun","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5004-2194","authenticated-orcid":false,"given":"Guifang","family":"Dou","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Anhui Medical University, Hefei 230032, China"},{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuchen","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Anhui Medical University, Hefei 230032, China"},{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e347","DOI":"10.1161\/CIR.0000000000001209","article-title":"2024 Heart Disease and Stroke Statistics: A Report of US and Global Data from the American Heart Association","volume":"149","author":"Martin","year":"2024","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e004996","DOI":"10.1161\/JAHA.116.004996","article-title":"Association between Modifiable Risk Factors and Pharmaceutical Expenditures among Adults with Atherosclerotic Cardiovascular Disease in the United States: 2012\u20132013 Medical Expenditures Panel Survey","volume":"6","author":"Salami","year":"2017","journal-title":"J. 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