The Effect of Autophagy on Chronic Intermittent Hypobaric Hypoxia Ameliorating Liver Damage in Metabolic Syndrome Rats.

ABSTRACT: Aim:Our previous study demonstrated that chronic intermittent hypobaric hypoxia (CIHH) can confer hepatic protection by reducing endoplasmic reticulum stress (ERS) in high-fat-high-fructose induced metabolic syndrome (MS) rats. It is known that there is a functional coupling between autophagy and ERS. This study aimed to investigate the effect of CIHH on autophagy function and adenosine mono-phosphate-activated protein kinase-mammalian target of rapamycin (AMPK?-mTOR) signaling pathway in hepatic tissue of MS rats. Main Methods:6-week old male Sprague-Dawley rats were randomly divided into: control (CON), CIHH (treated with hypobaric hypoxia simulating 5000-m altitude for 28 days, 6 h daily), MS (induced by 16-week high fat diet and 10% fructose water feeding), and MS + CIHH groups (exposed to CIHH after 16-week MS model). Food and water intakes, body weight, Lee's index, fat coefficient, systolic arterial pressure, blood biochemicals, and histopathology of liver were measured, the expression of phosphorylated (p)-AMPK, p-mTOR, autophagy-related and ERS-related proteins were assayed in hepatic tissue. Key Findings:The MS rats displayed obesity, hypertension, polydipsia, glucose and lipids metabolism disorders, increased inflammatory cytokine, hepatic tissue morphological and functional damage, and the up-regulated expressions of ERS-related, autophagy-related proteins and p-mTOR, and the down-regulated expression of p-AMPK?. All aforementioned abnormalities in MS rats were ameliorated in MS + CIHH rats. Significance:In conclusion CIHH confers hepatic protection through activating AMPK-mTOR signaling pathway and the autophagy function, thus inhibiting ERS in hepatic tissue.

SUBMITTER: Cui F 

PROVIDER: S-EPMC7002389 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature