{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:13:08Z","timestamp":1753891988464,"version":"3.41.2"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T00:00:00Z","timestamp":1703116800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Background and aims:<\/jats:bold> The serum metabolites changes in patients with hepatitis B virus (HBV)-related cirrhosis as progression. Peroxisome proliferator-activated receptor gamma (PPAR\u03b3) is closely related to lipid metabolism in cirrhotic liver. However, the relationship between fatty acids and the expression of hepatic PPAR\u03b3 during cirrhosis regression remains unknown. In this study, we explored the serum metabolic characteristics and expression of PPAR\u03b3 in patients with histological response to treatment with entecavir.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Sixty patients with HBV-related cirrhosis were selected as the training cohort with thirty patients each in the regression (R) group and non-regression (NR) group based on their pathological changes after 48-week treatment with entecavir. Another 72 patients with HBV-related cirrhosis and treated with entecavir were collected as the validation cohort. All of the serum samples were tested using ultra-performance liquid chromatography coupled to tandem mass spectrometry. Data were processed through principal component analysis and orthogonal partial least square discriminant analysis. Hepatic PPAR\u03b3 expression was observed using immunohistochemistry. The relationship between serum fatty acids and PPAR\u03b3 was calculated using Pearson\u2019s or Spearman\u2019s correlation analysis.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> A total of 189 metabolites were identified and 13 differential metabolites were screened. Compared to the non-regression group, the serum level of fatty acids was higher in the R group. At baseline, the expression of PPAR\u03b3 in hepatic stellate cells was positively correlated with adrenic acid (<jats:italic>r<\/jats:italic><jats:sup>2<\/jats:sup> = 0.451, <jats:italic>p<\/jats:italic> = 0.046). The expression of PPAR\u03b3 in both groups increased after treatment, and the expression of PPAR\u03b3 in the R group was restored in HSCs much more than that in the NR group (<jats:italic>p<\/jats:italic> = 0.042). The adrenic acid and arachidonic acid (AA) in the R group also upgraded more than the NR group after treatment (<jats:italic>p<\/jats:italic> = 0.037 and 0.014).<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Baseline serum differential metabolites, especially fatty acids, were identified in patients with HBV-related cirrhosis patients who achieved cirrhosis regression. Upregulation of adrenic acid and arachidonic acid in serum and re-expression of PPAR\u03b3 in HSCs may play a crucial role in liver fibrosis improvement.<\/jats:p>","DOI":"10.3389\/fphar.2023.1329266","type":"journal-article","created":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T04:13:19Z","timestamp":1703131999000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Serum metabolomics characteristics and fatty-acid-related mechanism of cirrhosis with histological response in chronic hepatitis B"],"prefix":"10.3389","volume":"14","author":[{"given":"Hai-Na","family":"Fan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi-Min","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Ning","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun-Kai","family":"Dai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng-Hai","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,12,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1186\/s12944-017-0437-2","article-title":"Serum lipid profile as a marker of liver impairment in hepatitis B Cirrhosis patients","volume":"16","author":"Arain","year":"2017","journal-title":"Lipids Health Dis."},{"key":"B2","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1007\/s12272-010-0313-3","article-title":"Selective inhibition of activated stellate cells and protection from carbon tetrachloride-induced liver injury in rats by a new PPARgamma agonist KR62776","volume":"33","author":"Bae","year":"2010","journal-title":"Arch. 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