文章基本信息

标题：Differential Expression of Ormdl Genes in the Islets of Mice and Humans with Obesity
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作者：Hugo Lee ; Rachel J. Fenske ; Tugce Akcan 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：7
页码：1-17
DOI：10.1016/j.isci.2020.101324
语种：English
出版社：Elsevier
摘要：SummaryThe orosomucoid-like (Ormdl) proteins play a critical role in sphingolipid homeostasis, inflammation, and ER stress, all of which are associated with obesity and βcell dysfunction. However, their roles in β cells and obesity remain unknown. Here, we show that islets from overweight/obese human donors displayed marginally reducedORMDL1-2expression, whereasORMDL3expression was significantly downregulated compared with islets from lean donors. In contrast,Ormdl3was substantially upregulated in the islets of leptin-deficient obese (ob/ob) mice compared with lean mice. Treatment ofob/obmice and their islets with leptin markedly reduced isletOrmld3expression.Ormdl3knockdown in a β cell line induced expression of pro-apoptotic markers, which was rescued by ceramide synthase inhibitor fumonisin B1. Our results reveal differential expression ofOrmdl3in the islets of a mouse model and humans with obesity, highlight the potential effect of leptin in this differential regulation, and suggest a role forOrmdl3in β cell apoptosis.Graphical AbstractDisplay OmittedHighlights•Islets of overweight/obese human donors display markedly reducedORMDL3expression•Ormdl3expression was significantly upregulated in the islets ofob/obmice•Leptin treatment markedly reducedOrmld3expression in the islets ofob/obmice•Fumonisin B1 restores increased apoptotic marker levels induced byOrmdl3silencingBiological Sciences; Endocrinology