{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:17:46Z","timestamp":1790533066781,"version":"4.1.0"},"reference-count":65,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2019,7,15]],"date-time":"2019-07-15T00:00:00Z","timestamp":1563148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008799","name":"Gilead Foundation","doi-asserted-by":"publisher","award":["Gilead Fellowship 2015"],"award-info":[{"award-number":["Gilead Fellowship 2015"]}],"id":[{"id":"10.13039\/100008799","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Since nutrition might have a significant impact on liver function, we analyzed the early effect of Western-type diet on hepatic tissue and lipid and drug metabolism in Wistar\u2013Kyoto rats (n = 8); eight rats fed with a standard diet were used as controls. Histological analysis of liver tissue was performed, and plasma biochemical parameters were measured. Plasma concentration of six bile acids was determined by ultra-liquid chromatography-tandem mass spectrometry UHPLC-MS\/MS. Hepatic gene expressions of enzymes involved in drug and lipid metabolism were assessed by means of real-time reverse transcription (qRT)-PCR. Liver of rats fed with a Western diet did not show macroscopic histological alterations, but number and diameter of lipid droplets increased, as well as DGAT1, GPAT4, SCD, FASN and SREBP2 expression. Furthermore, Western diet-fed animals showed an increase in the activation of hepatic stellate cells and macrophage number in liver tissue, as well as a significant increase in AST and bilirubin levels (p &lt; 0.01), and in the LDL:HDL cholesterol ratio (p &lt; 0.001). Plasma chenodeoxycholic acid concentration increased significantly, whereas cholic acid decreased (p &lt; 0.05), and cytochrome P450 genes were generally downregulated. Significant changes in hepatic lipid and drug metabolism are early induced by the Western diet, prior to steatosis development. Such changes are associated with a peculiar alteration in circulating bile acids, which could represent an early marker of non-alcoholic fatty liver disease (NAFLD) development.<\/jats:p>","DOI":"10.3390\/nu11071602","type":"journal-article","created":{"date-parts":[[2019,7,16]],"date-time":"2019-07-16T02:23:16Z","timestamp":1563243796000},"page":"1602","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Western Diet-Induced Metabolic Alterations Affect Circulating Markers of Liver Function before the Development of Steatosis"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2247-8227","authenticated-orcid":false,"given":"Daniela","family":"Gabbia","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padova, L.go Meneghetti 2, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1264-8878","authenticated-orcid":false,"given":"Marco","family":"Roverso","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences, University of Padova, via Marzolo 1, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Guido","sequence":"additional","affiliation":[{"name":"Department of Medicine, General Pathology and Cytopathology Unit, University of Padova, via Giustiniani 2, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Sacchi","sequence":"additional","affiliation":[{"name":"Department of Medicine, General Pathology and Cytopathology Unit, University of Padova, via Giustiniani 2, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Scaffidi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padova, L.go Meneghetti 2, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Carrara","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padova, L.go Meneghetti 2, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genny","family":"Orso","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padova, L.go Meneghetti 2, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4127-8941","authenticated-orcid":false,"given":"Francesco Paolo","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Surgery, Oncology and Gastroenterology, University of Padova, via Giustiniani 2, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annarosa","family":"Floreani","sequence":"additional","affiliation":[{"name":"Department of Surgery, Oncology and Gastroenterology, University of Padova, via Giustiniani 2, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9152-3602","authenticated-orcid":false,"given":"Sara","family":"Bogialli","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences, University of Padova, via Marzolo 1, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6398-8237","authenticated-orcid":false,"given":"Sara","family":"De Martin","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padova, L.go Meneghetti 2, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S0140-6736(11)60614-4","article-title":"Type 2 diabetes across generations: From pathophysiology to prevention and management","volume":"378","author":"Nolan","year":"2011","journal-title":"Lancet Lond. 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