Milk Exosomes from Gestational Diabetes Mellitus (GDM) and Healthy Parturient Exhibit Differential miRNAs Profiles and Distinct Regulatory Bioactivity on Hepatocyte Proliferation

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 parturien...

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Bibliographic Details
Published in:Molecular nutrition & food research 2023-08, Vol.67 (16), p.e2300005-n/a
Main Authors: Zheng, Zhongdaixi, Mo, Jiaqi, Lin, Fengjuan, Wang, Jiexian, Chen, Junbin, Luo, Huiyu, Liu, Yuguo, Su, Chuhong, Gu, Xiangfu, Xiong, Fei, Zha, Longying
Format: Article
Language:English
Subjects:
Biological activity
Breast milk
CD9 antigen
Cell proliferation
Diabetes mellitus
Exosomes
Gestational diabetes
gestational diabetes mellitus
hepatocyte proliferation
Hepatocytes
human milk
Insulin
miRNAs
Rapamycin
TOR protein
Ultracentrifugation
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Summary: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. Milk exosomes from gestational diabetes mellitus (GDM) and healthy parturient have similar morphology and phenotype. Milk exosomes from GDM parturient harbor richer and more diverse miRNAs. Milk exosomes from GDM and healthy parturient do not influence insulin sensitivity. Milk exosomes from GDM inhibit hepatocyte proliferation by delivering miR‐101‐3p.
ISSN:1613-4125
1613-4133
DOI:10.1002/mnfr.202300005