期刊
HUMAN CELL
卷 34, 期 6, 页码 1697-1708出版社
SPRINGER JAPAN KK
DOI: 10.1007/s13577-021-00593-1
关键词
Human umbilical cord-derived mesenchymal stem cells; Exosomes; miR-627-5p; FTO; Glucose and lipid metabolism; Insulin tolerance; Liver damage; Non-alcoholic fatty liver disease
类别
资金
- National Key R&D Program of China, Synthetic Biology Research [2019YFA0904500]
- National Natural Science Foundation of China [81860151]
- Key R&D Program of Jiangxi Province [20192BBG70027]
The study found that hUC-MSCs-derived exosomal miR-627-5p improved glucose and lipid metabolism, alleviated liver damage, and reduced lipid deposition in NAFLD rats by targeting FTO. Exosomal miR-627-5p also reduced body weight, liver weight, and liver index in NAFLD rats, suggesting the potential of hUC-MSCs-exosomes as a treatment for NAFLD.
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 PPAR alpha 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 alleviate liver damage by repressing FTO expression, thereby ameliorating NAFLD progression. Thus, hUC-MSCs-exosomes may be a potential treatment for NAFLD.
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