Human umbilical cord-derived mesenchymal stem cell-exosomal miR-627-5p ameliorates non-alcoholic fatty liver disease by repressing FTO expression.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver disorders. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs)-based therapy is currently considered to be an effective treatment for NAFLD. The present study aimed to determine whether hUC-MSCs-exosomes have a hepatoprotective effect on NAFLD. We constructed NAFLD rat model by high-fat high-fructose feeding. Liver cells (L-O2) were treated with palmitic acid (PA) to mimic NAFLD model. NAFLD rats and PA-treated L-O2 cells were treated with hUC-MSCs-exosomes, and then we determined the influence of exosomes on liver damage and glucose and lipid metabolism in vivo and in vitro. We found that hUC-MSCs-exosomes exhibited an up-regulation of miR-627-5p. Exosomal miR-627-5p promoted cell viability and repressed apoptosis of PA-treated L-O2 cells. Exosomal miR-627-5p also enhanced the expression of G6Pc, PEPCK, FAS and SREBP-1c and suppressed PPARα expression in PA-treated L-O2 cells. Moreover, miR-627-5p interacted with fat mass and obesity-associated gene (FTO) and inhibited FTO expression in L-O2 cells. MiR-627-5p-enriched exosomes improved glucose and lipid metabolism in L-O2 cells by targeting FTO. In vivo, exosomal miR-627-5p ameliorated insulin tolerance, liver damage, glucose and lipid metabolism and reduced lipid deposition in NAFLD rats. Exosomal miR-627-5p also reduced body weight, liver weight, and liver index (body weight/liver weight) in NAFLD rats. In conclusion, these data demonstrate that HUC-MSCs-derived exosomal miR-627-5p improves glucose and lipid metabolism and alleviateliver damage by repressing FTO expression, thereby ameliorating NAFLD progression. Thus, hUC-MSCs-exosomes may be a potential treatment for NAFLD.