{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:16:46Z","timestamp":1783487806151,"version":"3.55.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"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. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The major cause of non-alcoholic fatty liver disease (NAFLD) is obesity; in fact, this condition has been defined as metabolic dysfunction-associated steatotic liver disease (MASLD). Non-invasive diagnosis and grading of NAFLD are the subjects of the studies. Cytokeratin-18 (CK-18) is particularly highlighted as an indicator of liver cell death and steatohepatitis, but its relationship with obesity remains unclear. This study aimed to evaluate the metabolic parameters, CK-18 levels, and liver histopathology in high-fat diet-induced obesity in rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Rats were fed either a normal-fat diet (NFD) or a high-fat diet (HFD) for eight weeks. Body weights, metabolic-liver parameters and CK-18 levels were assessed at study end. The liver histopathological changes (steatosis, lobular inflammation, ballooning, fibrosis) and NAFLD activity score were examined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Increased final body weight (335.8\u00a0\u00b1\u00a020.2 vs 291.5\u00a0\u00b1\u00a06.25 g; p&amp;lt;0.001), glucose (186.4\u00a0\u00b1\u00a046.9 vs 130.0\u00a0\u00b1\u00a016.2 mg\/dL; p=0.011), insulin (4.30\u00a0\u00b1\u00a00.70 vs 2.23\u00a0\u00b1\u00a00.82 IU\/L; p&amp;lt;0.001), HOMA-IR (2.03\u00a0\u00b1\u00a00.79 vs 0.73\u00a0\u00b1\u00a00.34; p=0.003), ALT (72.34\u00a0\u00b1\u00a012.35 vs 55.43\u00a0\u00b1\u00a05.75 U\/L; p=0.009) and CK-18 (1.46\u00a0\u00b1\u00a00.18 vs 0.88\u00a0\u00b1\u00a00.18 ng\/mL; p&amp;lt;0.001) levels and decreased AST\/ALT ratio (1.16\u00a0\u00b1\u00a00.09 vs 1.32\u00a0\u00b1\u00a00.14; p=0.020) were observed in HFD group compared to NFD group. Histologically, all HFD specimens showed ballooning (8\/8) and half showed steatosis (4\/8). NAFLD score remained \u22643 in all specimens nevertheless CK-18 values tended to co-occur with higher ALT levels and ballooning formation within the HFD group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclus\u0131on<\/jats:title>\n                    <jats:p>HFD-induced obesity was associated with increased CK-18 and the hepatocellular changes as remarkable ballooning without the overt steatohepatitis. These findings support CK-18 interpreting as a signal for early hepatocellular injury in obesity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1853417","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T04:49:06Z","timestamp":1783486146000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cytokeratin-18 increase as a signal for early liver cell changes in high-fat diet-induced obesity before overt steatohepatitis"],"prefix":"10.3389","volume":"17","author":[{"given":"\u00d6zlem","family":"\u00d6zdemir","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Medicine Faculty of Ordu University","place":["Ordu, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c7a\u011fr\u0131","family":"Akal\u0131n","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Medicine Faculty of Ordu University","place":["Ordu, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuat","family":"Ekiz","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology. 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Medicine Faculty of Samsun University","place":["Samsun, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orhan","family":"Ba\u015f","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Medicine Faculty of Ordu University","place":["Ordu, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmet","family":"Bayrak","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Medicine Faculty of Ordu University","place":["Ordu, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeliz","family":"Ka\u015fko Ar\u0131c\u0131","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Medicine Faculty of Ordu University","place":["Ordu, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"B1","unstructured":"Newsroom \/ Obesity and Overweight\n         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