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Fenofibrate attenuates fatty acid-induced islet β-cell dysfunction and apoptosis via inhibiting the NF-κB/MIF dependent inflammatory pathway.
- Source :
-
Metabolism: clinical and experimental [Metabolism] 2017 Dec; Vol. 77, pp. 23-38. Date of Electronic Publication: 2017 Sep 20. - Publication Year :
- 2017
-
Abstract
- Background: Fatty acid-induced lipotoxicity and macrophage migration inhibitory factor (MIF) affect pancreatic β-cell function, and may promote the development of diabetes mellitus. However, the association of lipotoxicity with MIF and the effect of Fenofibrate on β-cell function remain unknown.<br />Methods: LPL+/- mice and MIN6 cells stimulated with palmitic acid (PA) were utilized as models of lipid metabolism disorders. Factors associated with insulin secretion and apoptosis were assessed in the presence or absence of Fenofibrate. The possible mechanisms of lipotoxicity-induced β-cell dysfunction were also explored.<br />Results: Fenofibrate effectively improved lipid accumulation in pancreatic β-cells, increased glucose-stimulated insulin secretion and β-cell mass, and significantly downregulated pro-apoptotic molecules, at the gene and protein levels, both in vivo and in vitro. Additionally, elevated MIF levels in serum from LPL+/- mice and PA-treated MIN6 cells were starkly decreased after Fenofibrate administration. Mechanistic analysis indicated that NF-κB signaling was remarkably triggered, which could further activate MIF transcription. Furthermore, Fenofibrate exerted beneficial effects on fatty acid-induced β-cell dysfunction likely by inhibiting the NF-κB/MIF dependent inflammatory response.<br />Conclusions: Fenofibrate ameliorates lipotoxicity-induced β-cell dysfunction and apoptosis by inhibiting the NF-κB/MIF inflammatory pathway. These findings provide novel insights into the treatment of lipotoxicity-induced metabolic disorders.<br /> (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Apoptosis drug effects
B-Lymphocytes cytology
Fatty Acids pharmacology
Fenofibrate therapeutic use
Hypolipidemic Agents pharmacology
Hypolipidemic Agents therapeutic use
Inflammation prevention & control
Intramolecular Oxidoreductases metabolism
Islets of Langerhans pathology
Islets of Langerhans physiopathology
Macrophage Migration-Inhibitory Factors metabolism
Mice
NF-kappa B metabolism
B-Lymphocytes drug effects
Fenofibrate pharmacology
Islets of Langerhans drug effects
Signal Transduction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1532-8600
- Volume :
- 77
- Database :
- MEDLINE
- Journal :
- Metabolism: clinical and experimental
- Publication Type :
- Academic Journal
- Accession number :
- 28941594
- Full Text :
- https://doi.org/10.1016/j.metabol.2017.09.001