Differential Expression of Ormdl Genes in the Islets of Mice and Humans with Obesity
Summary: The 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 hu...
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doaj-e4129b60719e479c8bf64f74152ff2022020-11-25T03:38:38ZengElsevieriScience2589-00422020-07-01237101324Differential Expression of Ormdl Genes in the Islets of Mice and Humans with ObesityHugo Lee0Rachel J. Fenske1Tugce Akcan2Elliot Domask3Dawn B. Davis4Michelle E. Kimple5Feyza Engin6Department of Biomolecular Chemistry, University of Wisconsin-Madison, School of Medicine and Public Health, WI 53706, USAInterdepartmental Graduate Program in Nutritional Sciences, Madison, WI 53706, USA; Department of Medicine, Division of Endocrinology, Diabetes & Metabolism, University of Wisconsin-Madison, School of Medicine and Public Health, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USADepartment of Biomolecular Chemistry, University of Wisconsin-Madison, School of Medicine and Public Health, WI 53706, USADepartment of Biomolecular Chemistry, University of Wisconsin-Madison, School of Medicine and Public Health, WI 53706, USADepartment of Medicine, Division of Endocrinology, Diabetes & Metabolism, University of Wisconsin-Madison, School of Medicine and Public Health, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USAInterdepartmental Graduate Program in Nutritional Sciences, Madison, WI 53706, USA; Department of Medicine, Division of Endocrinology, Diabetes & Metabolism, University of Wisconsin-Madison, School of Medicine and Public Health, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA; Department of Cell and Regenerative Biology, Madison, WI 53705, USA; Department of Academic Affairs, University of Wisconsin-Madison, Madison, WI 53705, USADepartment of Biomolecular Chemistry, University of Wisconsin-Madison, School of Medicine and Public Health, WI 53706, USA; Department of Medicine, Division of Endocrinology, Diabetes & Metabolism, University of Wisconsin-Madison, School of Medicine and Public Health, WI 53705, USA; Corresponding authorSummary: The 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 reduced ORMDL1-2 expression, whereas ORMDL3 expression was significantly downregulated compared with islets from lean donors. In contrast, Ormdl3 was substantially upregulated in the islets of leptin-deficient obese (ob/ob) mice compared with lean mice. Treatment of ob/ob mice and their islets with leptin markedly reduced islet Ormld3 expression. Ormdl3 knockdown 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 of Ormdl3 in the islets of a mouse model and humans with obesity, highlight the potential effect of leptin in this differential regulation, and suggest a role for Ormdl3 in β cell apoptosis.http://www.sciencedirect.com/science/article/pii/S2589004220305113Biological SciencesEndocrinology |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hugo Lee Rachel J. Fenske Tugce Akcan Elliot Domask Dawn B. Davis Michelle E. Kimple Feyza Engin |
spellingShingle |
Hugo Lee Rachel J. Fenske Tugce Akcan Elliot Domask Dawn B. Davis Michelle E. Kimple Feyza Engin Differential Expression of Ormdl Genes in the Islets of Mice and Humans with Obesity iScience Biological Sciences Endocrinology |
author_facet |
Hugo Lee Rachel J. Fenske Tugce Akcan Elliot Domask Dawn B. Davis Michelle E. Kimple Feyza Engin |
author_sort |
Hugo Lee |
title |
Differential Expression of Ormdl Genes in the Islets of Mice and Humans with Obesity |
title_short |
Differential Expression of Ormdl Genes in the Islets of Mice and Humans with Obesity |
title_full |
Differential Expression of Ormdl Genes in the Islets of Mice and Humans with Obesity |
title_fullStr |
Differential Expression of Ormdl Genes in the Islets of Mice and Humans with Obesity |
title_full_unstemmed |
Differential Expression of Ormdl Genes in the Islets of Mice and Humans with Obesity |
title_sort |
differential expression of ormdl genes in the islets of mice and humans with obesity |
publisher |
Elsevier |
series |
iScience |
issn |
2589-0042 |
publishDate |
2020-07-01 |
description |
Summary: The 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 reduced ORMDL1-2 expression, whereas ORMDL3 expression was significantly downregulated compared with islets from lean donors. In contrast, Ormdl3 was substantially upregulated in the islets of leptin-deficient obese (ob/ob) mice compared with lean mice. Treatment of ob/ob mice and their islets with leptin markedly reduced islet Ormld3 expression. Ormdl3 knockdown 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 of Ormdl3 in the islets of a mouse model and humans with obesity, highlight the potential effect of leptin in this differential regulation, and suggest a role for Ormdl3 in β cell apoptosis. |
topic |
Biological Sciences Endocrinology |
url |
http://www.sciencedirect.com/science/article/pii/S2589004220305113 |
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