Academic Journal
Effects of Exendin-4 on human adipose tissue inflammation and ECM remodelling
| العنوان: | Effects of Exendin-4 on human adipose tissue inflammation and ECM remodelling |
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| المؤلفون: | Pastel, E, Joshi, S, Knight, B, Liversedge, N, Ward, R, Kos, K |
| بيانات النشر: | Nature Publishing Group |
| سنة النشر: | 2016 |
| المجموعة: | University of Exeter: Open Research Exeter (ORE) |
| الوصف: | This is the final version of the article. Available from the publisher via the DOI in this record. ; BACKGROUND/OBJECTIVES: Subjects with type-2 diabetes are typically obese with dysfunctional adipose tissue (AT). Glucagon-like peptide-1 (GLP-1) analogues are routinely used to improve glycaemia. Although, they also aid weight loss that improves AT function, their direct effect on AT function is unclear. To explore GLP-1 analogues' influence on human AT's cytokine and extracellular matrix (ECM) regulation, we therefore obtained and treated omental (OMAT) and subcutaneous (SCAT) AT samples with Exendin-4, an agonist of the GLP-1 receptor (GLP-1R). SUBJECTS/METHODS: OMAT and abdominal SCAT samples obtained from women during elective surgery at the Royal Devon & Exeter Hospital (UK) were treated with increasing doses of Exendin-4. Changes in RNA expression of adipokines, inflammatory cytokines, ECM components and their regulators were assessed and protein secretion analysed by ELISA. GLP-1R protein accumulation was compared in paired AT depot samples. RESULTS: Exendin-4 induced an increase in OMAT adiponectin (P=0.02) and decrease in elastin expression (P=0.03) in parallel with reduced elastin secretion (P=0.04). In contrast to OMAT, we did not observe an effect on SCAT. There was no change in the expression of inflammatory markers (CD14, TNFA, MCP-1), collagens, TGFB1 or CTGF. GLP-1R accumulation was higher in SCAT. CONCLUSIONS: Independently of weight loss, which may bias findings of in vivo studies, GLP-1 analogues modify human OMAT physiology favourably by increasing the insulin-sensitising cytokine adiponectin. However, the reduction of elastin and no apparent effect on AT's inflammatory cytokines suggest that GLP-1 analogues may be less beneficial to AT function, especially if there is no associated weight loss. ; This programme was supported by the European Federation for the Study of Diabetes (EFSD/GSK 09). |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | https://www.ncbi.nlm.nih.gov/pubmed/27941938; Vol. 6, e235; nutd201644; http://hdl.handle.net/10871/26498; Nutrition and Diabetes; PMC5223133 |
| DOI: | 10.1038/nutd.2016.44 |
| الاتاحة: | http://hdl.handle.net/10871/26498 https://doi.org/10.1038/nutd.2016.44 |
| Rights: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/ by/4.0/ © The Author(s) 2016 |
| رقم الانضمام: | edsbas.C8B487EE |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/nutd.2016.44 |
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