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 (AMPKα-mTOR) signaling pathway in hepatic tissue of MS rats.
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.
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-AMPKα. All aforementioned abnormalities in MS rats were ameliorated in MS + CIHH rats.
In conclusion CIHH confers hepatic protection through activating AMPK-mTOR signaling pathway and the autophagy function, thus inhibiting ERS in hepatic tissue.