PMID- 37357556 OWN - NLM STAT- MEDLINE DCOM- 20230817 LR - 20230907 IS - 1613-4133 (Electronic) IS - 1613-4125 (Linking) VI - 67 IP - 16 DP - 2023 Aug TI - Milk Exosomes from Gestational Diabetes Mellitus (GDM) and Healthy Parturient Exhibit Differential miRNAs Profiles and Distinct Regulatory Bioactivity on Hepatocyte Proliferation. PG - e2300005 LID - 10.1002/mnfr.202300005 [doi] AB - SCOPE: Exosomes, a novel type of bioactive component in human milk (HM), affect infant development, growth, and health. Recent studies indicate that HM exosomes and miRNAs relate to gestational diabetes mellitus (GDM). However, the miRNAs profiles and functionalities of HM exosomes from GDM parturient remain unclear. This study aims to compare the differential miRNAs in HM exosomes from GDM and healthy parturient, and investigate the HM exosomes bioactivities in regulating hepatocyte proliferation and insulin sensitivity. METHODS AND RESULTS: This study extracted HM exosomes from GDM (GDM-EXO) and healthy (NOR-EXO) parturient by ultracentrifugation, high-throughput sequenced and compared the exosomal miRNAs profiles, and explored the regulatory bioactivities on hepatocyte proliferation in HepG2 cells and Balb/c mice. As compared to NOR-EXO, GDM-EXO has similar morphology, size, concentration, and exosome-specific markers (CD9 and TSG101) expression. GDM-EXO and NOR-EXO specifically harbor 1299 and 8 miRNAs, respectively. Moreover, GDM-EXO had 176 upregulated and 47 downregulated miRNAs compared with NOR-EXO. Both GDM-EXO and NOR-EXO were absorbed in cultured HepG2 hepatocytes and mice liver. GDM-EXO inhibited hepatocytes proliferation by downregulating mammalian target of rapamycin (mTOR) possibly via exosomal miR-101-3p delivery. CONCLUSION: HM exosomes from GDM and healthy parturient exhibit differential miRNAs profiles and distinct regulatory bioactivity on hepatocyte proliferation. CI - (c) 2023 Wiley-VCH GmbH. FAU - Zheng, Zhongdaixi AU - Zheng Z AD - Department of Nutrition and Food Hygiene, School of Public Health, National Medical Products Administration (NMPA) Key Laboratory for Safety Evaluation of Cosmetics, Guangdong Provincial Key Laboratory of Tropical Disease Research, Southern Medical University, Guangzhou, Guangdong, 510515, P. R. China. AD - Department of Environmental Health, School of Public Health, National Medical Products Administration (NMPA) Key Laboratory for Safety Evaluation of Cosmetics, Guangdong Provincial Key Laboratory of Tropical Disease Research, Southern Medical University, Guangzhou, Guangdong, 510515, P. R. China. FAU - Mo, Jiaqi AU - Mo J AD - Department of Nutrition and Food Hygiene, School of Public Health, National Medical Products Administration (NMPA) Key Laboratory for Safety Evaluation of Cosmetics, Guangdong Provincial Key Laboratory of Tropical Disease Research, Southern Medical University, Guangzhou, Guangdong, 510515, P. R. China. FAU - Lin, Fengjuan AU - Lin F AD - Department of Nutrition and Food Hygiene, School of Public Health, National Medical Products Administration (NMPA) Key Laboratory for Safety Evaluation of Cosmetics, Guangdong Provincial Key Laboratory of Tropical Disease Research, Southern Medical University, Guangzhou, Guangdong, 510515, P. R. China. FAU - Wang, Jiexian AU - Wang J AD - Department of Nutrition and Food Hygiene, School of Public Health, National Medical Products Administration (NMPA) Key Laboratory for Safety Evaluation of Cosmetics, Guangdong Provincial Key Laboratory of Tropical Disease Research, Southern Medical University, Guangzhou, Guangdong, 510515, P. R. China. FAU - Chen, Junbin AU - Chen J AD - Department of Nutrition and Food Hygiene, School of Public Health, National Medical Products Administration (NMPA) Key Laboratory for Safety Evaluation of Cosmetics, Guangdong Provincial Key Laboratory of Tropical Disease Research, Southern Medical University, Guangzhou, Guangdong, 510515, P. R. China. FAU - Luo, Huiyu AU - Luo H AD - Department of Nutrition and Food Hygiene, School of Public Health, National Medical Products Administration (NMPA) Key Laboratory for Safety Evaluation of Cosmetics, Guangdong Provincial Key Laboratory of Tropical Disease Research, Southern Medical University, Guangzhou, Guangdong, 510515, P. R. China. FAU - Liu, Yuguo AU - Liu Y AD - Department of Nutrition and Food Hygiene, School of Public Health, National Medical Products Administration (NMPA) Key Laboratory for Safety Evaluation of Cosmetics, Guangdong Provincial Key Laboratory of Tropical Disease Research, Southern Medical University, Guangzhou, Guangdong, 510515, P. R. China. FAU - Su, Chuhong AU - Su C AD - Department of Nutrition and Food Hygiene, School of Public Health, National Medical Products Administration (NMPA) Key Laboratory for Safety Evaluation of Cosmetics, Guangdong Provincial Key Laboratory of Tropical Disease Research, Southern Medical University, Guangzhou, Guangdong, 510515, P. R. China. FAU - Gu, Xiangfu AU - Gu X AD - Department of Nutrition and Food Hygiene, School of Public Health, National Medical Products Administration (NMPA) Key Laboratory for Safety Evaluation of Cosmetics, Guangdong Provincial Key Laboratory of Tropical Disease Research, Southern Medical University, Guangzhou, Guangdong, 510515, P. R. China. FAU - Xiong, Fei AU - Xiong F AD - Department of Nutrition and Food Hygiene, School of Public Health, National Medical Products Administration (NMPA) Key Laboratory for Safety Evaluation of Cosmetics, Guangdong Provincial Key Laboratory of Tropical Disease Research, Southern Medical University, Guangzhou, Guangdong, 510515, P. R. China. FAU - Zha, Longying AU - Zha L AUID- ORCID: 0000-0002-2648-2162 AD - Department of Nutrition and Food Hygiene, School of Public Health, National Medical Products Administration (NMPA) Key Laboratory for Safety Evaluation of Cosmetics, Guangdong Provincial Key Laboratory of Tropical Disease Research, Southern Medical University, Guangzhou, Guangdong, 510515, P. R. China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230625 PL - Germany TA - Mol Nutr Food Res JT - Molecular nutrition & food research JID - 101231818 RN - 0 (MicroRNAs) SB - IM MH - Pregnancy MH - Female MH - Animals MH - Mice MH - Child MH - Humans MH - *Diabetes, Gestational/genetics MH - Milk MH - *Exosomes/metabolism MH - *MicroRNAs/genetics/metabolism MH - Hepatocytes/metabolism MH - Cell Proliferation MH - Mammals/metabolism OTO - NOTNLM OT - exosomes OT - gestational diabetes mellitus OT - hepatocyte proliferation OT - human milk OT - miRNAs EDAT- 2023/06/26 06:41 MHDA- 2023/08/17 06:42 CRDT- 2023/06/26 03:09 PHST- 2023/03/27 00:00 [revised] PHST- 2023/01/05 00:00 [received] PHST- 2023/08/17 06:42 [medline] PHST- 2023/06/26 06:41 [pubmed] PHST- 2023/06/26 03:09 [entrez] AID - 10.1002/mnfr.202300005 [doi] PST - ppublish SO - Mol Nutr Food Res. 2023 Aug;67(16):e2300005. doi: 10.1002/mnfr.202300005. Epub 2023 Jun 25.