{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T02:38:15Z","timestamp":1773715095099,"version":"3.50.1"},"reference-count":46,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T00:00:00Z","timestamp":1739836800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82260810"],"award-info":[{"award-number":["82260810"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>PEG400 is widely used as a pharmaceutical excipient in the biomedical field. Increasing evidence suggests that PEG400 is not an inert drug carrier; it can influence the activity of various drug-metabolizing enzymes and transporters, thereby affecting the in vivo process of drugs. It can also alleviate obesity and adipose tissue inflammation induced by a high-fat diet. In this study, we employed proteomics to investigate the impact of PEG400 on hepatic protein expression in rats. We found that over 40 metabolic enzymes were altered, with UDP-glucuronosyltransferase 1a9 (Ugt1a9) showing the most significant upregulation. This observation is consistent with our previous findings. KEGG pathway enrichment analysis revealed that PEG400 influences retinol metabolism, steroid hormone biosynthesis, drug metabolism, bile secretion, fatty acid degradation, peroxisome proliferator-activated receptor (PPAR) signaling pathway, and pentose and glucuronate interconversions. Western blot and molecular docking were used to quantitatively analyze related proteins. The results demonstrated that PEG400 promotes the metabolism of retinol to produce retinoic acid; enhances bile secretion by upregulating bile acid synthesis and transporter proteins; and activates the PPAR\u03b1 signaling pathway to regulate the expression of fat metabolism-related proteins, thereby reducing lipid accumulation. Furthermore, as natural ligands for nuclear receptors, retinoic acid and bile acids may activate nuclear receptors and initiate the regulation of target gene expression. We found upregulation of the nuclear receptors PPAR\u03b1, retinoid X receptor alpha (RXR\u03b1), and pregnane X receptor (PXR). RXR\u03b1 can form a dimer with PPAR\u03b1 or PXR to regulate the expression of target genes, which may explain the changes in the expression of numerous metabolic enzymes. This study provides a comprehensive understanding of the effects of PEG400 on liver metabolism in rats, reveals its potential biological functions, and offers new insights into the application and development of PEG400.<\/jats:p>","DOI":"10.3390\/ijms26041732","type":"journal-article","created":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T03:47:06Z","timestamp":1739850426000},"page":"1732","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Proteomics Profiling Reveals Pharmaceutical Excipient PEG400 Induces Nuclear-Receptor-Activation-Affected Lipid Metabolism and Metabolic Enzyme Expression"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1585-253X","authenticated-orcid":false,"given":"Mei","family":"Zhao","sequence":"first","affiliation":[{"name":"School of Basic Medicine & State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine & School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 561113, China"},{"name":"Microbiology and Biochemical Pharmaceutical Engineering Center of Guizhou Provincial Department of Education, Guizhou Medical University, Guiyang 561113, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siyuan","family":"Cao","sequence":"additional","affiliation":[{"name":"School of Basic Medicine & State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine & School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 561113, China"},{"name":"Microbiology and Biochemical Pharmaceutical Engineering Center of Guizhou Provincial Department of Education, Guizhou Medical University, Guiyang 561113, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine & State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine & School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 561113, China"},{"name":"Microbiology and Biochemical Pharmaceutical Engineering Center of Guizhou Provincial Department of Education, Guizhou Medical University, Guiyang 561113, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leyuan","family":"Shang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine & State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine & School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 561113, China"},{"name":"Microbiology and Biochemical Pharmaceutical Engineering Center of Guizhou Provincial Department of Education, Guizhou Medical University, Guiyang 561113, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ye","family":"Hang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine & State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine & School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 561113, China"},{"name":"Microbiology and Biochemical Pharmaceutical Engineering Center of Guizhou Provincial Department of Education, Guizhou Medical University, Guiyang 561113, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pengjiao","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine & State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine & School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 561113, China"},{"name":"Microbiology and Biochemical Pharmaceutical Engineering Center of Guizhou Provincial Department of Education, Guizhou Medical University, Guiyang 561113, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuo","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine & State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine & School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 561113, China"},{"name":"Microbiology and Biochemical Pharmaceutical Engineering Center of Guizhou Provincial Department of Education, Guizhou Medical University, Guiyang 561113, China"},{"name":"Experimental Animal Center, Guizhou Medical University, Guiyang 561113, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1277-1206","authenticated-orcid":false,"given":"Chaoji","family":"Li","sequence":"additional","affiliation":[{"name":"School of Basic Medicine & State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine & School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 561113, China"},{"name":"Microbiology and Biochemical Pharmaceutical Engineering Center of Guizhou Provincial Department of Education, Guizhou Medical University, Guiyang 561113, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine & State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine & School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 561113, China"},{"name":"Microbiology and Biochemical Pharmaceutical Engineering Center of Guizhou Provincial Department of Education, Guizhou Medical University, Guiyang 561113, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiuli","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Basic Medicine & State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine & School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 561113, China"},{"name":"Microbiology and Biochemical Pharmaceutical Engineering Center of Guizhou Provincial Department of Education, Guizhou Medical University, Guiyang 561113, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2535","DOI":"10.2174\/092986706778201648","article-title":"Drug excipients","volume":"13","author":"Antal","year":"2006","journal-title":"Curr. 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