Perilipin 2 Protects against Lipotoxicity-Induced Islet Fibrosis by Inducing Islet Stellate Cell Activation Phenotype Changes. (6th July 2022)

• Record Type: Journal Article
• Authors: Zhou, Yunting; Wang, Yuming; Ni, Chengming; Wang, Huiying; Zhou, Junming; Wan, Bingying; Li, Huiqin; Li, Fengfei; Huang, Rong; Xu, Wei; Shan, Ting; Cai, Tingting; Kong, Xiaoceng; Liu, Bingli; Liu, Xiaomei; Sun, Zilin; Ma, Jianhua
• Other Names: Szczepankiewicz Dawid Academic Editor.
• Is Part Of: BioMed research international. Volume 2022(2022)
• Publication Date: 2022-07-06
• Subjects: Medicine -- Periodicals; Biology -- Periodicals; Biotechnology -- Periodicals; Life sciences -- Periodicals; 610.5
• DOI: 10.1155/2022/4581405
• Languages: English
• ISSNs: 2314-6133

Abstract

Abstract : Aims. We explored whether and how perilipin 2 ( Plin2 ) protected islets against lipotoxicity-induced islet dysfunction by regulating islet stellate cells (ISCs) activation. Methods. Six-week-old male rats were given a high-fat diet or a control diet for 28 weeks. Glucose metabolic phenotypes were assessed using glucose/insulin tolerance tests, masson, and immunohistochemical staining. ISCs activation levels were assessed from rats and palmitic acid- (PA-) treated cultured ISCs by immunofluorescence, Oil red O staining, electron microscopy, quantitative PCR, and western blotting. Changes in ISCs phenotype of activation degree and its underlying mechanisms were assessed by target gene lentiviral infection, high-performance liquid chromatography (HPLC), and western blotting. Results. Obese rats showed glucose intolerance, decreased endocrine hormone profiles, and elevated expression of α -smooth muscle actin ( α -SMA), a polygonal appearance without cytoplasmic lipid droplets of ISCs in rats and isolated islets. PA-treated cultured ISCs exhibited faster proliferation and migration abilities with the induction of mRNA levels of lipid metabolism proteins, especially Plin2 . The overexpression of Plin2 resulted in ISCs "re-quiescent" phenotypes associated with inhibition of the Smad3-TGF- β signaling pathways. Conclusions. Our observations suggest a protective role of Plin2 in weakening ISCs activation. It may serve as a novel therapeutic target for preventing islet fibrosis for T2DM.