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Pleurotus abieticola, an edible lignin-degrading fungus, remains relatively understudied in terms of its bioactivity and medicinal properties. In this study, the lipid-lowering effect of Pleurotus abieticola polysaccharide (PAPS1) was systematically explored in high-fat diet (HFD)-induced HLP mice. The findings demonstrated that the administration of PAPS1 significantly inhibited bodyweight gain, ameliorated blood glucose and lipid levels, reduced fat accumulation, and mitigated hepatic injury in HLP mice. In addition, PAPS1 demonstrated the capability to increase the levels of three distinct fecal metabolites while simultaneously reducing the levels of eight other fecal metabolites in HLP mice. According to biological detection, PAPS1 reduced the hepatic level of reactive oxygen species (ROS) and pro-inflammatory factors, such as tumor necrosis factor (TNF)-\u03b1 and interleukin (IL)-1\u03b2, -6, -17A, -22, and -23, and increased the expression of anti-inflammatory factor IL-10. Combined with proteomics, Western blot and immunohistochemistry analysis showed that PAPS1 exerted suppressive effects on inflammation and oxidative damage by inhibiting the nuclear factor-\u03baB (NF-\u03baB)\/signal transducer and activator of transcription 3 (STAT3) signaling pathway in HLP mice. These findings offer evidence supporting the effectiveness of PAPS1 as a therapeutic agent in reducing lipid levels through its targeting of chronic inflammation.<\/jats:p>","DOI":"10.3390\/nu15234904","type":"journal-article","created":{"date-parts":[[2023,11,24]],"date-time":"2023-11-24T03:43:59Z","timestamp":1700797439000},"page":"4904","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Pleurotus abieticola Polysaccharide Alleviates Hyperlipidemia Symptoms via Inhibition of Nuclear Factor-\u03baB\/Signal Transducer and Activator of Transcription 3-Mediated Inflammatory Responses"],"prefix":"10.3390","volume":"15","author":[{"given":"Yongfeng","family":"Zhang","sequence":"first","affiliation":[{"name":"Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjie","family":"Lin","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keyi","family":"Wu","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Jiang","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Mudanjiang Normal University, Mudanjiang 157011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanzhou","family":"Li","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7066","DOI":"10.1039\/D3FO01451G","article-title":"The anti-hyperlipidemic effect and underlying mechanisms of barley (Hordeum vulgare L.) grass polysaccharides in mice induced by a high-fat diet","volume":"14","author":"Yan","year":"2023","journal-title":"Food Funct."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"12686","DOI":"10.1039\/D2FO01746F","article-title":"Whole grain benefit: Synergistic effect of oat phenolic compounds and \u03b2-glucan on hyperlipidemia via gut microbiota in high-fat-diet mice","volume":"13","author":"Li","year":"2022","journal-title":"Food Funct."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1016\/j.fshw.2023.02.021","article-title":"The protective effects of Levilactobacillus brevis FZU0713 on lipid metabolism and intestinal microbiota in hyperlipidemic rats","volume":"12","author":"Fan","year":"2023","journal-title":"Food Sci. 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