Perilipin5 protects against lipotoxicity and alleviates endoplasmic reticulum stress in pancreatic β-cells.
Background: Chronic exposure of pancreatic β-cells to excess free fatty acids is thought to contribute to type 2 diabetes pathogenesis in obesity by impairing β-cell function and even leading to apoptosis. In β-cells, lipid droplet-associated protein perilipin 5 (PLIN5) has been shown to enhance ins...
| Publicado en: | Nutrition & Metabolism Vol. 16; no. 1 |
|---|---|
| Autores principales: | , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
BioMed Central
7/30/2019
|
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=137792786&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 137792786 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 17437075 1CYX jtl: Nutrition & Metabolism issn: 17437075 maglogo: N pubinfo: dt: 7/30/2019 vid: 16 iid: 1 pid: 24147 pub: BioMed Central artinfo: ui: 137792786 137792786 137792786 10.1186/s12986-019-0375-2 137792786 ppct: 1 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Perilipin5 protects against lipotoxicity and alleviates endoplasmic reticulum stress in pancreatic β-cells. aug: au: Zhu, Yunxia Zhang, Xiaoyan Zhang, Li Zhang, Mingliang Li, Ling Luo, Deng Zhong, Yuan affil: Department of Geriatrics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No.600, Yishan Road, 200233, Shanghai, China sug: subj: Carrier Proteins Metabolism Fatty Acids Metabolism Oxidation-Reduction Endoplasmic Reticulum Stress, Physiological Islets of Langerhans Metabolism Animal Studies Mice Apoptosis Diabetes Mellitus, Type 2 Insulin Cell Viability Biological Assay Analysis of Variance T-Tests ab: Background: Chronic exposure of pancreatic β-cells to excess free fatty acids is thought to contribute to type 2 diabetes pathogenesis in obesity by impairing β-cell function and even leading to apoptosis. In β-cells, lipid droplet-associated protein perilipin 5 (PLIN5) has been shown to enhance insulin secretion by regulating intracellular lipid metabolism; the roles of PLIN5 in response to lipotoxicity remain poorly understood. Methods: INS-1 β-cells were transfected with PLIN5-overexpression adenovirus (Ad-PLIN5) and treated with palmitate. C57BL/6 J male mice were fed with high fat diet and tail intravenous injected with adeno-associated virus overexpressing PLIN5 (AAV-PLIN5) in β-cells. Results: Our data showed that palmitate and PPAR agonists including WY14643 (PPARα), GW501516 (PPARβ/δ), rosiglitazone (PPARγ) in vitro all induced PLIN5 expression in INS-1 cells. Under palmitate overload, although upregulating PLIN5 promoted lipid droplet storage, it alleviated lipotoxicity in INS-1 β-cells with improved cell viability, cell apoptosis and β-cell function. The protection role of PLIN5 in β-cell function observed in cell experiments were further verified in in vivo study indicated by mitigated glucose intolerance in high fat diet fed mice with β-cell-specific overexpression of PLIN5. Mechanistic experiments revealed that enhanced FAO induced by elevation of PLIN5, followed by decreased ER stress may be a major mechanism responsible for alleviation of lipotoxicity observed in the present study. Conclusions: Our finding substantiated the important role of PLIN5 in protection against lipotoxicity in β-cells. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|