20.500.12556/RUL-147069 Differential alternative polyadenylation response to high-fat diet between polygenic obese and healthy lean mice Obesity's complex etiology due to the interplay of environment and genetics makes it a more challenging research and health problem. Some of the contributing genetic factors that have not yet been examined in detail entail mRNA polyadenylation (PA). Genes with multiple PA sites express mRNA isoforms differing in coding sequence or 3′UTR through alternative polyadenylation (APA). Alterations in PA have been associated with various diseases; however, its contribution to obesity is not well-researched. Following an 11-week high-fat diet, the APA sites in the hypothalamus of two unique mouse models for polygenic obesity (Fat line) and healthy leanness (Lean line) were determined using whole transcriptome termini site sequencing (WTTS-seq). We found 17 genes of interest with differentially expressed APA (DE-APA) isoforms, among which seven were previously associated with obesity or obesity-related traits (Pdxdc1, Smyd3, Rpl14, Copg1, Pcna, Ric3, Stx3) but have not yet been studied in the context of APA. The remaining ten genes (Ccdc25, Dtd2, Gm14403, Hlf, Lyrm7, Mrpl3, Pisd-ps3, Sbsn, Slx1b, Spon1) represent novel candidates associated with obesity/adiposity due to variability brought about by differential usage of APA sites. Our results provide insights into the relationship between PA and the hypothalamus in the context of obesity, by being the first study of DE-APA sites and DE-APA isoforms in these mouse models. Future studies are needed further to explore the role of APA isoforms in polygenic obesity by expanding the scope of research to other metabolically important tissues (such as liver and adipose tissues) and investigating the potential for targeting PA as a therapeutic strategy for obesity management. hypothalamus alternative polyadenylation APA fat and lean selection mouse lines differentially expressed alternative polyadenylation sites DE-APA laboratorijske miši poligeni modeli debela linija vitka linija genetika poliadenilacija prehrana živali krma maščobe true false true Angleški jezik Slovenski jezik Članek v reviji 2023-06-22 09:18:01 2023-06-22 09:18:02 2023-10-23 08:36:44 0000-00-00 00:00:00 2023 0 0 Str. 83-91 Vol. 666 2023 0000-00-00 Zaloznikova Objavljeno apc 0000-00-00 0000-00-00 0000-00-00 575 1090-2104 10.1016/j.bbrc.2023.05.005 150686467 1-s2.0-S0006291X23005612-main.pdf 1-s2.0-S0006291X23005612-main.pdf 1 C0E6A80BF54DCBB322A496B999DDA679 915d6aeb7390ee51112eb7f112b6f477dcdaa8d01913e335c6406cb83919e8da e5e857bf-10d3-11ee-a314-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=170421 https://www.sciencedirect.com/science/article/pii/S0006291X23005612 0 8c561b2a-10cc-11ee-a314-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=170419 Biotehniška fakulteta 0 0 0