{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:19:07Z","timestamp":1770337147244,"version":"3.49.0"},"reference-count":56,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Chronic liver injury is accompanied by coordinated disturbances in lipid trafficking and inflammatory\u2013fibrogenic signaling. Transforming growth factor beta 1 (TGF-\u03b21) signaling has been implicated in hepatic fibrogenesis and tumor-associated remodeling and may co-vary with disturbances in lipid trafficking. Lisosan G (LG), a fermented wheat-derived nutraceutical, has reported antioxidant and anti-inflammatory activity and may influence these interconnected pathways. This study evaluated whether dietary LG alters the lipid composition of plasma lipoprotein fractions and hepatic TGF-\u03b21 levels across distinct liver contexts. Seventy-two female Wistar rats were randomized into nine groups (n = 8\/group) defined by liver condition, consisting of healthy control (Control), non-neoplastic liver (PH), and neoplastic liver injury (HCC; PH followed by diethylnitrosamine, DEN), and diet (standard diet, SD + 2.5% LG, or SD + 5% LG). Plasma lipoproteins (VLDL, LDL, HDL1, HDL2) were isolated by stepwise KBr density-gradient ultracentrifugation, and cholesterol (TC), phospholipids (PL), and triacylglycerols (TG) were quantified in each fraction. Hepatic TGF-\u03b21 was measured by ELISA and normalized to total protein. LG effects depended strongly on baseline liver status, with significant Condition \u00d7 Diet interactions for most lipid endpoints and for hepatic TGF-\u03b21. In healthy rats, LG produced fraction-selective remodeling rather than uniform lipid lowering, including increased VLDL-TG at both doses and non-linear changes in cholesterol distribution across LDL and HDL subfractions. After PH, LG broadened lipid remodeling, including reduced VLDL-PL, increased VLDL-TG (both doses), and an increase in LDL-TC at 5% LG, accompanied by marked changes in HDL1\/HDL2 cholesterol partitioning. In HCC, LG induced pronounced, often dose-dependent increases in LDL-associated lipids (LDL-PL, LDL-TG, LDL-TC) and increased HDL1-TC while decreasing HDL2-TC. Hepatic TGF-\u03b21 was elevated in PH and further increased in HCC versus controls; LG reduced hepatic TGF-\u03b21 in a condition-dependent manner, with the strongest reduction at 5% LG in HCC. Dietary Lisosan G remodels circulating lipoprotein lipid composition in a liver-status-dependent manner and is associated with reduced hepatic TGF-\u03b21 abundance in injured liver, most prominently in neoplastic injury. These findings are consistent with the notion that nutraceutical interventions may show stronger phenotypic effects under perturbed metabolic\u2013fibrogenic states than under stable physiology, while highlighting the need for mechanistic work to distinguish altered lipoprotein secretion from changes in peripheral clearance and to assess pathway-level TGF-\u03b2 signaling.<\/jats:p>","DOI":"10.3390\/biology15030284","type":"journal-article","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T11:13:01Z","timestamp":1770289981000},"page":"284","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lisosan G as a Modulator of Serum Lipid\/Lipoprotein Changes, Lipid Metabolism and TGF-\u03b21 Level in Neoplastic and Non-Neoplastic Liver Injury: A Rat Model Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3115-3267","authenticated-orcid":false,"given":"Bart\u0142omiej","family":"Szymczak","sequence":"first","affiliation":[{"name":"Sub-Department of Pathophysiology, Department of Preclinical Veterinary Sciences, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, Akademicka 12, 20-033 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7530-7814","authenticated-orcid":false,"given":"Luisa","family":"Pozzo","sequence":"additional","affiliation":[{"name":"Institute of Agricultural Biology and Biotechnology, National Research Council, Via Moruzzi 1, 56124 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2039-2908","authenticated-orcid":false,"given":"Szymon","family":"Zmorzy\u0144ski","sequence":"additional","affiliation":[{"name":"Institute of Human Sciences, Faculty of Health Sciences, Academy of Zamo\u015b\u0107, Pereca Street 2, 22-400 Zamo\u015b\u0107, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1148-6515","authenticated-orcid":false,"given":"Anna","family":"Wilczy\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Epizootiology and Clinic of Infectious Diseases, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, 20-612 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1823-2865","authenticated-orcid":false,"given":"Andrea","family":"Vornoli","sequence":"additional","affiliation":[{"name":"Institute of Agricultural Biology and Biotechnology, National Research Council, Via Moruzzi 1, 56124 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Lutnicka","sequence":"additional","affiliation":[{"name":"Medical Faculty-Student, the J.P. II Catholic University of Lublin, 20-708 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3903-1141","authenticated-orcid":false,"given":"Marta","family":"W\u00f3jcik","sequence":"additional","affiliation":[{"name":"Oncology Lab, Department of Epizootiology and Clinic of Infectious Diseases, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, 20-612 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e292","DOI":"10.3346\/jkms.2024.39.e292","article-title":"Global, Re-gional, and National Trends in Liver Disease-Related Mortality Across 112 Countries From 1990 to 2021, With Pro-jections to 2050: Comprehensive Analysis of the WHO Mortality Database","volume":"39","author":"Hahn","year":"2024","journal-title":"J. Korean Med. 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