PMID- 34410623 OWN - NLM STAT- MEDLINE DCOM- 20220125 LR - 20240226 IS - 1749-0774 (Electronic) IS - 0914-7470 (Linking) VI - 34 IP - 6 DP - 2021 Nov TI - Human umbilical cord-derived mesenchymal stem cell-exosomal miR-627-5p ameliorates non-alcoholic fatty liver disease by repressing FTO expression. PG - 1697-1708 LID - 10.1007/s13577-021-00593-1 [doi] AB - 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 PPARalpha 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. CI - (c) 2021. Japan Human Cell Society. FAU - Cheng, Lidan AU - Cheng L AD - Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Donghu District, Nanchang, 330006, China. AD - Institute for the Study of Endocrinology and Metabolism in Jiangxi Province, Nanchang, 330006, China. FAU - Yu, Peng AU - Yu P AD - Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Donghu District, Nanchang, 330006, China. AD - Institute for the Study of Endocrinology and Metabolism in Jiangxi Province, Nanchang, 330006, China. FAU - Li, Fangfang AU - Li F AD - Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Donghu District, Nanchang, 330006, China. AD - Institute for the Study of Endocrinology and Metabolism in Jiangxi Province, Nanchang, 330006, China. FAU - Jiang, Xueling AU - Jiang X AD - Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Donghu District, Nanchang, 330006, China. AD - Institute for the Study of Endocrinology and Metabolism in Jiangxi Province, Nanchang, 330006, China. FAU - Jiao, Xiaojuan AU - Jiao X AD - Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Donghu District, Nanchang, 330006, China. AD - Institute for the Study of Endocrinology and Metabolism in Jiangxi Province, Nanchang, 330006, China. FAU - Shen, Yunfeng AU - Shen Y AUID- ORCID: 0000-0003-3404-8400 AD - Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Donghu District, Nanchang, 330006, China. syf92@live.com. AD - Institute for the Study of Endocrinology and Metabolism in Jiangxi Province, Nanchang, 330006, China. syf92@live.com. FAU - Lai, Xiaoyang AU - Lai X AD - Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Donghu District, Nanchang, 330006, China. laixiay@outlook.com. AD - Institute for the Study of Endocrinology and Metabolism in Jiangxi Province, Nanchang, 330006, China. laixiay@outlook.com. LA - eng GR - 81860151/National Natural Science Foundation of China/ GR - 2019YFA0904500/National Key R&D Program of China, Synthetic Biology Research/ GR - 20192BBG70027/Key R&D Program of Jiangxi Province/ PT - Journal Article DEP - 20210819 PL - Japan TA - Hum Cell JT - Human cell JID - 8912329 RN - 0 (MIRN627 microRNA, human) RN - 0 (MicroRNAs) RN - EC 1.14.11.33 (Alpha-Ketoglutarate-Dependent Dioxygenase FTO) RN - EC 1.14.11.33 (FTO protein, human) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Alpha-Ketoglutarate-Dependent Dioxygenase FTO/*genetics/*metabolism MH - Animals MH - Cell Line MH - Cell- and Tissue-Based Therapy/*methods MH - Disease Models, Animal MH - Exosomes/*genetics/physiology MH - Gene Expression/*genetics MH - Glucose/metabolism MH - Humans MH - Lipid Metabolism/genetics MH - Male MH - *Mesenchymal Stem Cell Transplantation MH - MicroRNAs/*administration & dosage/*genetics/metabolism/physiology MH - Non-alcoholic Fatty Liver Disease/*genetics/*therapy MH - Rats, Sprague-Dawley MH - Umbilical Cord/*cytology MH - Rats OTO - NOTNLM OT - Exosomes OT - FTO OT - Glucose and lipid metabolism OT - Human umbilical cord-derived mesenchymal stem cells OT - Insulin tolerance OT - Liver damage OT - Non-alcoholic fatty liver disease OT - miR-627-5p EDAT- 2021/08/20 06:00 MHDA- 2022/01/27 06:00 CRDT- 2021/08/19 12:34 PHST- 2021/03/04 00:00 [received] PHST- 2021/08/11 00:00 [accepted] PHST- 2021/08/20 06:00 [pubmed] PHST- 2022/01/27 06:00 [medline] PHST- 2021/08/19 12:34 [entrez] AID - 10.1007/s13577-021-00593-1 [pii] AID - 10.1007/s13577-021-00593-1 [doi] PST - ppublish SO - Hum Cell. 2021 Nov;34(6):1697-1708. doi: 10.1007/s13577-021-00593-1. Epub 2021 Aug 19.