Diabetes, Metabolic Syndrome and Obesity (Nov 2020)
Adiponectin Protects Obese Rats from Aggravated Acute Lung Injury via Suppression of Endoplasmic Reticulum Stress
Abstract
Ke Wei,1 Jie Luo,1 Jun Cao,1 Lihua Peng,1 Li Ren,1 Fan Zhang2 1Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Department of Anesthesiology, Jianyang People’s Hospital, Jianyang, Sichuan 641400, People’s Republic of ChinaCorrespondence: Ke WeiDepartment of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, 1# Youyi Road, Yuzhong District, Chongqing, People’s Republic of ChinaTel +86 23 89011069Fax +86 23 89011062Email [email protected]: Endoplasmic reticulum (ER) stress seems to mediate the obesity-induced susceptibility to acute lung injury (ALI). The present study was designed to evaluate the role of ER stress in adiponectin (APN)-induced lung protection in an obese rat model treated with lipopolysaccharide (LPS).Methods: Four-week-old male Sprague-Dawley rats fed either a normal chow diet or a high-fat diet for 12 weeks were randomly assigned to one of the following groups: lean rats, diet-induced obesity rats, lean rats with ALI, obese rats with ALI, obese rats pretreated with 4-phenylbutyric acid (4-PBA) before ALI or obese rats pretreated with APN before ALI. At 24 h after instillation of LPS into the lungs, cell counts in the bronchoalveolar lavage fluid (BALF) were determined. Lung tissues were separated to assess the degree of inflammation, pulmonary oedema, epithelial apoptosis and the expression of ER stress marker proteins.Results: The 78-kDa glucose-regulated protein (GRP78) and C/EBP homologous protein (CHOP) expression in the lung tissues of obese rats was upregulated before ALI, as well as the elevated apoptosis in epithelial cells. During ALI, the expression of ER stress marker proteins was similarly increased in both lean and obese rats, while significant downregulation of Mitofusin 2 (MFN2) was detected in obese epithelial cells. The lung tissues of obese rats showed higher concentrations of tumor necrosis factor-alpha (TNF-α), Interleukin 6 (IL-6) and IL-10, enhanced neutrophil counts and elevated wet/dry weight ratios. APN and 4-PBA decreased the degree of ER stress and suppressed LPS-induced lung inflammation, pulmonary oedema and epithelial apoptosis.Conclusion: APN may exert protective effects against the exacerbated lung injuries in obese rats by attenuating ER stress, which operates as a key molecular pathway in the progression of ALI.Keywords: adiponectin, endoplasmic reticulum stress, obesity, lung injury
