Activation of PPARγ Protects Obese Mice from Acute Lung Injury by Inhibiting Endoplasmic Reticulum Stress and Promoting Mitochondrial Biogenesis. (28th September 2022)

• Record Type: Journal Article
• Authors: Tang, Yin; Wei, Ke; Liu, Ling; Ma, Jingyue; Wu, Siqi; Tang, Wenjing
• Other Names: Mandard Stéphane Academic Editor.
• Is Part Of: PPAR research. Volume 2022(2022)
• Publication Date: 2022-09-28
• Subjects: Peroxisomes -- Periodicals; Peroxisomal disorders -- Periodicals; 571.65505
• DOI: 10.1155/2022/7888937
• Languages: English
• ISSNs: 1687-4757

Abstract

Abstract : Objective . Obesity-induced endoplasmic reticulum (ER) stress plays a role in increased susceptibility to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). The activation of peroxisome proliferator-activated receptor- γ (PPAR γ ) is associated with lung protection and is effective in ameliorating ER stress and mitochondrial dysfunction. The aim of this study was to investigate the expression of PPAR γ in the lung tissues of obese mice and explore whether the PPAR γ -dependent pathway could mediate decreased ALI/ARDS by regulating ER stress and mitochondrial biogenesis. Methods . We determined PPAR γ expression in the lung tissues of normal and obese mice. ALI models of alveolar epithelial cells and of obese mice were used and treated with either PPAR γ activator rosiglitazone (RSG) or PPAR γ inhibitor GW9662. Lung tissue and cell samples were collected to assess lung inflammation and apoptosis, and ER stress and mitochondrial biogenesis were detected. Results . PPAR γ expression was significantly decreased in the lung tissue of obese mice compared with that in normal mice. Both in vivo and in vitro studies have shown that activation of PPAR γ leads to reduced expression of the ER stress marker proteins 78-kDa glucose-regulated protein (GRP78), C/EBP homologous protein (CHOP), and Caspase12. Conversely, expression of the mitochondrial biogenesis-related proteins peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1 α ), nuclear respiratory factor-1 (NRF-1), and mitochondrial transcription factor A (TFAM) increased. Furthermore, activation of PPAR γ is associated with decreased levels of lung inflammation and epithelial apoptosis and increased expression of adiponectin (APN) and mitofusin2 (MFN2). GW9662 bound to PPAR γ and blocked its transcriptional activity and then diminished the protective effect of PPAR γ on lung tissues. Conclusions . PPAR γ activation exerts anti-inflammation effects in alveolar epithelia by alleviating ER stress and promoting mitochondrial biogenesis. Therefore, lower levels of PPAR γ in the lung tissues of obese mice may lead to an increased susceptibility to ALI.