{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:06:34Z","timestamp":1787504794296,"version":"build-2736575974"},"reference-count":43,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation Project","doi-asserted-by":"publisher","award":["32460829"],"award-info":[{"award-number":["32460829"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Introduction: Mn is a trace element essential for growth and development in organisms, and adequate Mn levels are crucial for maintaining normal liver function. This study aimed to investigate the effects of Mn deficiency on the liver and elucidate the underlying mechanisms using transcriptomics. Methods: Weanling mice were fed a Mn-deficient diet, and Mn chloride (MnCl2) was administered intraperitoneally to correct the deficiency. Liver pathological changes were evaluated through histological examination. Liver function and key lipid metabolism markers were assessed using biochemical assays, while hepatic oxidative stress levels were measured via flow cytometry and biochemical kits. Alterations in inflammatory factors were detected using ELISA and qPCR. The mechanisms underlying Mn\u2019s effects on liver function were further explored through Western blot, qPCR, and transcriptome sequencing. Results: Mn deficiency impaired liver morphology and structure. Serum levels of ALT, AST, and ALP were significantly elevated, while ALB decreased, confirming hepatic dysfunction. This dysfunction led to oxidative stress, characterized by increased hepatic ROS and MDA levels, alongside reduced Mn-SOD, GSH-Px, and T-AOC activities. Additionally, Mn deficiency elevated serum TG, TC, and LDL-C levels, indicating abnormal lipid metabolism. Hepatic pro-inflammatory factors (IL-6, IL-1\u03b2, and TNF-\u03b1) were significantly upregulated. Transcriptomic analysis revealed distinct gene expression patterns under different Mn conditions, with KEGG pathway analysis identifying the PPAR signaling pathway as a key regulatory target. Conclusions: Our findings suggest a potential pathogenic cascade in which manganese deficiency may initially induce hepatic oxidative stress, potentially leading to suppression of the PPAR signaling pathway. This inhibition of PPAR\u03b1\/\u03b3 could subsequently orchestrate downstream manifestations of aberrant lipid metabolism and inflammatory responses. Thus, the PPAR signaling pathway is proposed as a plausible central hub for translating oxidative damage into metabolic and inflammatory dysfunction in the manganese-deficient liver.<\/jats:p>","DOI":"10.3390\/nu17193030","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T10:27:53Z","timestamp":1758623273000},"page":"3030","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Effects of Mn Deficiency on Hepatic Oxidative Stress, Lipid Metabolism, Inflammatory Response, and Transcriptomic Profile in Mice"],"prefix":"10.3390","volume":"17","author":[{"given":"Yaodong","family":"Hu","sequence":"first","affiliation":[{"name":"College of Animal Science, Xichang University, Xichang 615000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi","family":"Tang","sequence":"additional","affiliation":[{"name":"College of Animal Science, Xichang University, Xichang 615000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silu","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Animal Science, Xichang University, Xichang 615000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caiyun","family":"Sun","sequence":"additional","affiliation":[{"name":"College of Animal Science, Xichang University, Xichang 615000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binlong","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Animal Science, Xichang University, Xichang 615000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binjian","family":"Cai","sequence":"additional","affiliation":[{"name":"College of Animal Science, Xichang University, Xichang 615000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Yin","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Agri-Forestry, Southwest University of Science and Technology, Mianyang 621010, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7580707","DOI":"10.1155\/2018\/7580707","article-title":"The Essential Element Manganese, Oxidative Stress, and Metabolic Diseases: Links and Interactions","volume":"2018","author":"Li","year":"2018","journal-title":"Oxidative Med. 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