Melatonin prevents chronic intermittent hypoxia-induced injury by inducing sirtuin 1-mediated autophagy in steatotic liver of mice

Hepatic steatosis that occasionally

These results suggest that melatonin could ameliorate FD/CIH-induced hepatocellular damage by activating SIRT1-mediated autophagy signaling.

A high-fat diet (FD)-induced obesity mouse model was subjected to intermittent hypoxia/normoxia events for approximately 8 h per day using an autophagy agonist, rapamycin, or an inhibitor, 3-methyladenine (3-MA), and SRT1720, a sirtuin 1 (SIRT1) activator, or sirtinol, a SIRT1 inhibitor, with or without melatonin for a total of six successive weeks, followed by assessment of expression of autophagy-related genes and activity of serum aminotransferase as well as histological evaluation of tissue morphology.

This study was aimed to evaluate the role of CIH in steatohepatitis progression and the regulatory function of melatonin on fatty liver sensitivity to CIH injury, mainly focusing on autophagy signaling.

Neither FD nor CIH alone causes significant liver injury; however, the combination yielded higher serum aminotransferase activities and more severe histological changes, accompanied by a decrease in autophagy activity. Melatonin markedly inhibited FD/CIH-stimulated liver injury by enhancing autophagy. In contrast, SIRT1 inhibition resulted in a decrease in the expression of melatonin-induced autophagy-related genes as well as diminished its protective effects on FD/CIH-induced liver injury.