MicroRNA-122-5p Inhibition Improves Inflammation and Oxidative Stress Damage in Dietary-Induced Non-alcoholic Fatty Liver Disease Through Targeting FOXO3

Abstract

Misregulated microRNA network has been emerging as the main regulator in non-alcoholic fatty liver disease (NAFLD). The deregulation of miR-122-5p is associated with the liver disease. However, the specific role and molecular mechanism of miR-122-5p in NAFLD remain unclear. In this study, we have reported that the high-fat diet (HFD) or palmitic acid (PA) significantly upregulated the hepatic miR-122-5p expression in vivo and in vitro. Inhibition of miR-122-5p suppressed accumulation-induced inflammation of lipids and oxidative stress damage in PA-treated L02 cells and HFD-induced fatty liver. The effect of the miR-122-5p inhibitor on NAFLD did not depend on insulin resistance-mediated PI3K/AKT/mammalian target of rapamycin (mTOR) signaling pathway but rather on the upregulation of its downstream FOXO3. Subsequently, we validated that miR-122-5p directly binds to the predicted 3′-UTR of FOXO3 to inhibit its gene expression. Conversely, silencing FOXO3 abolished the hepatic benefits of miR-122-5p inhibition to obese mice by decreasing the activity of antioxidant enzymes of superoxide dismutase (SOD). This study provides a novel finding that FOXO3 was the target gene of miR-122-5p to attenuate inflammatory response and oxidative stress damage in dietary-induced NAFLD. Our study provided evidence to reveal the physiological role of miR-122-5p in dietary-induced NAFLD.

Western diet-induced shifts in the maternal microbiome are associated with altered microRNA expression in baboon placenta and fetal liver

“…Both of these bacterial families are metabolically active members of the gut microbiome. MiR-122 accounts for around 70% of all miRNAs in the adult liver and plays a role in regulation of innate immunity (100), proliferation and differentiation of hepatocytes (101), lipid accumulation, and cholesterol metabolism (102). We found a differential association between fetal liver miR-122-5p and two maternal gut genera, Blautia and Ruminococcus, where Blautia negatively associated with miR-122-5p and Ruminococcus positively associated with miR-122-5p.…”

Association between Circulating MicroRNAs (miR-21-5p, miR-20a-5p, miR-29b-3p, miR-126-3p and miR-101-3p) and Chronic Allograft Dysfunction in Renal Transplant Recipients

“…As for miR-15a-5p and miR-122-5p, several studies have been published regarding fibrosis in different organs [ 54 , 55 , 56 , 57 ]. Liu et al compared different treatments involving rAAV-miR-122-5p and rAAV-GFP in 14-week-old male SHR and WKY rats.…”

Western diet-induced shifts in the maternal microbiome are associated with altered microRNA expression in baboon placenta and fetal liver

“…Both of these bacterial families are metabolically active members of the gut microbiome. MiR-122 accounts for around 70% of all miRNAs in the adult liver and plays a role in regulation of innate immunity (89), proliferation and differentiation of hepatocytes (90), lipid accumulation, and cholesterol metabolism (91). We found a differential association between fetal liver miR-122-5p and two maternal gut genera, Blautia and Ruminococcus , where Blautia negatively associated with miR-122-5p and Ruminococcus positively associated with miR-122-5p.…”