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We fed the mice with either a regular control diet (CD) or a WD. Standard glucose and insulin tolerance tests were performed, and body weight, plasma glucose, and triglyceride levels were measured to assess the glucose homeostasis in vivo. The WD induced obesity, glucose intolerance, and insulin resistance, with a fasting hyperglycemia. Further, we identified several changes in the gene expression of the analyzed candidate genes in all the examined target tissues, including the downregulation of Tcf7l2 in the liver, pancreas, white and brown adipose tissue (0.72, 0.56, 0.36, and 0.22-fold, respectively), in contrast to a marked upregulation in the intestine (2.57-fold). We also found downregulation of PPAR\u03b3 in the white and brown adipose tissue (0.55, 0.41-fold, respectively) and upregulation in the pancreas, liver, intestine, and skeletal muscle (1.25, 1.46, 1.97, and 2.59-fold, respectively). Our findings provide important insight into the characteristic pattern of changes in expression of candidate genes during the early stages of insulin resistance and glucose intolerance in this diet-induced mouse model of T2D.<\/jats:p>","DOI":"10.3390\/cimb47121053","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T15:41:12Z","timestamp":1765899672000},"page":"1053","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Western Diet Induces Changes in Gene Expression in Multiple Tissues During Early Insulin Resistance and Glucose Intolerance in Male C57BL\/6 Mice"],"prefix":"10.3390","volume":"47","author":[{"given":"Djordje","family":"Radulovi\u0107","sequence":"first","affiliation":[{"name":"Center for Human Genetics and Pharmacogenomics, Faculty of Medicine, University of Maribor, Taborska Ulica 8, 2000 Maribor, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3267-626X","authenticated-orcid":false,"given":"Jurij","family":"Dolen\u0161ek","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Faculty of Medicine, University of Maribor, Taborska Ulica 8, 2000 Maribor, Slovenia"},{"name":"Faculty of Natural Sciences and Mathematics, University of Maribor, Koro\u0161ka Cesta 160, 2000 Maribor, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andra\u017e","family":"Sto\u017eer","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Faculty of Medicine, University of Maribor, Taborska Ulica 8, 2000 Maribor, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1624-9428","authenticated-orcid":false,"given":"Uro\u0161","family":"Poto\u010dnik","sequence":"additional","affiliation":[{"name":"Center for Human Genetics and Pharmacogenomics, Faculty of Medicine, University of Maribor, Taborska Ulica 8, 2000 Maribor, Slovenia"},{"name":"Faculty of Natural Sciences and Mathematics, University of Maribor, Koro\u0161ka Cesta 160, 2000 Maribor, Slovenia"},{"name":"Laboratory for Biochemistry, Molecular Biology and Genomics, Faculty of Chemistry and Chemical Engineering, University of Maribor, Smetanova Ulica 17, 2345 Maribor, Slovenia"},{"name":"Department for Science and Research, University Medical Centre Maribor, Ljubljanska Ulica 5, 2000 Maribor, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1159\/000495665","article-title":"Beta Cell Functional Adaptation and Dysfunction in Insulin Resistance and the Role of Chronic Kidney Disease","volume":"143","author":"Stozer","year":"2019","journal-title":"Nephron"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1007\/s10654-018-0414-8","article-title":"Plant versus animal based diets and insulin resistance, prediabetes and type 2 diabetes: The Rotterdam Study","volume":"33","author":"Chen","year":"2018","journal-title":"Eur. 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