20.500.12556/DKUM-96976 Western diet induces changes in gene expression in multiple tissues during early insulin resistance and glucose intolerance in male C57BL/6 mice To better understand the molecular mechanisms by which a Western diet (WD) promotes the development of type 2 diabetes (T2D), we analyzed changes in the expression profiles of multiple glucose-regulatory tissues of male C57BL/6 mice. 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 PPARγ 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. dedifferentiation gene expression glucose-intolerant mice PPARγ Tcf7l2 type 2 diabetes Western diet true true true MDPI Angleški jezik Angleški jezik Znanstveno delo 2026-02-09 13:50:40 2026-02-09 13:54:13 2026-02-17 14:22:19 0000-00-00 00:00:00 2025 0 0 str. 1-25 Št. 12, št. članka 1053 Letn. 47 2025 0000-00-00 Zaloznikova Objavljeno apc 2025-12-05 2025-12-11 2025-12-16 616.379 261990915 10.3390/cimb47121053 1467-3045 RAZ_Radulovic_Djordje_2025.pdf RAZ_Radulovic_Djordje_2025.pdf 1 A02F5A9AC688528C18A1BA86C438C897 425c7af666ecd68ee761e5656e748d1cc529e4e618eb173cd22ba0df05034fa2 5fcabdfd-05b6-11f1-a772-00155d00019a https://dk.um.si/Dokument.php?lang=slv&id=203148 https://doi.org/10.3390/cimb47121053 1 f31ff3c3-05b5-11f1-a772-00155d00019a https://dk.um.si/Dokument.php?lang=slv&id=203146 https://www.mdpi.com/1467-3045/47/12/1053 1 f367a8b3-05b5-11f1-a772-00155d00019a https://dk.um.si/Dokument.php?lang=slv&id=203147 Medicinska fakulteta 0 0 0