PMID- 33197889
OWN - NLM
STAT- MEDLINE
DCOM- 20210427
LR  - 20210427
IS  - 1945-4589 (Electronic)
IS  - 1945-4589 (Linking)
VI  - 12
IP  - 22
DP  - 2020 Nov 10
TI  - Gonadal white adipose tissue-derived exosomal MiR-222 promotes obesity-associated 
      insulin resistance.
PG  - 22719-22743
LID - 10.18632/aging.103891 [doi]
AB  - In this study, we investigated the role of serum exosomal miR-222 in 
      obesity-related insulin resistance. Bioinformatics analyses showed that miR-222 
      levels were significantly upregulated in the white adipose tissue of obese 
      patients with insulin resistance (GSE25402 dataset) and in serum samples from 
      type 2 diabetes mellitus (T2DM) patients (GSE90028 dataset). Moreover, analysis 
      of miRNA expression in adipose tissue-specific Dicer knockout mice (GitHub 
      dataset) and diabetic model mice (GSE81976 and GSE85101 datasets), gonadal white 
      adipose tissue (gWAT) was the main source of serum exosomal miR-222. MiR-222 
      levels were significantly elevated in the serum, serum exosomes and gWAT of mice 
      fed a high-fat diet (HFD), and there was a corresponding downregulation of IRS1 
      and phospho-AKT levels in their liver and skeletal muscle tissues, which 
      correlated with impaired insulin sensitivity and glucose intolerance. These 
      effects were abrogated by surgically removing the gWAT from the HFD-fed mice. 
      Thus, gWAT-derived serum exosomal miR-222 appears to promote insulin resistance 
      in the liver and skeletal muscle of HFD-fed obese mice by suppressing IRS1 
      expression.
FAU - Li, Dameng
AU  - Li D
AD  - Nanjing DrumTower Hospital Center of Molecular Diagnostic and Therapy, State Key 
      Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center 
      for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences 
      (NAILS), NJU Institute of AI Biomedicine and Biotechnology, School of Life 
      Sciences, Nanjing University, Nanjing 210023, China.
FAU - Song, Huichen
AU  - Song H
AD  - Nanjing DrumTower Hospital Center of Molecular Diagnostic and Therapy, State Key 
      Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center 
      for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences 
      (NAILS), NJU Institute of AI Biomedicine and Biotechnology, School of Life 
      Sciences, Nanjing University, Nanjing 210023, China.
FAU - Shuo, Linghu
AU  - Shuo L
AD  - Nanjing DrumTower Hospital Center of Molecular Diagnostic and Therapy, State Key 
      Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center 
      for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences 
      (NAILS), NJU Institute of AI Biomedicine and Biotechnology, School of Life 
      Sciences, Nanjing University, Nanjing 210023, China.
FAU - Wang, Lei
AU  - Wang L
AD  - Nanjing DrumTower Hospital Center of Molecular Diagnostic and Therapy, State Key 
      Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center 
      for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences 
      (NAILS), NJU Institute of AI Biomedicine and Biotechnology, School of Life 
      Sciences, Nanjing University, Nanjing 210023, China.
FAU - Xie, Ping
AU  - Xie P
AD  - Nanjing DrumTower Hospital Center of Molecular Diagnostic and Therapy, State Key 
      Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center 
      for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences 
      (NAILS), NJU Institute of AI Biomedicine and Biotechnology, School of Life 
      Sciences, Nanjing University, Nanjing 210023, China.
FAU - Li, Weili
AU  - Li W
AD  - Nanjing DrumTower Hospital Center of Molecular Diagnostic and Therapy, State Key 
      Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center 
      for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences 
      (NAILS), NJU Institute of AI Biomedicine and Biotechnology, School of Life 
      Sciences, Nanjing University, Nanjing 210023, China.
FAU - Liu, Jiachen
AU  - Liu J
AD  - Nanjing DrumTower Hospital Center of Molecular Diagnostic and Therapy, State Key 
      Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center 
      for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences 
      (NAILS), NJU Institute of AI Biomedicine and Biotechnology, School of Life 
      Sciences, Nanjing University, Nanjing 210023, China.
FAU - Tong, Yafei
AU  - Tong Y
AD  - Nanjing DrumTower Hospital Center of Molecular Diagnostic and Therapy, State Key 
      Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center 
      for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences 
      (NAILS), NJU Institute of AI Biomedicine and Biotechnology, School of Life 
      Sciences, Nanjing University, Nanjing 210023, China.
FAU - Zhang, Chen-Yu
AU  - Zhang CY
AD  - Nanjing DrumTower Hospital Center of Molecular Diagnostic and Therapy, State Key 
      Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center 
      for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences 
      (NAILS), NJU Institute of AI Biomedicine and Biotechnology, School of Life 
      Sciences, Nanjing University, Nanjing 210023, China.
FAU - Jiang, Xiaohong
AU  - Jiang X
AD  - Nanjing DrumTower Hospital Center of Molecular Diagnostic and Therapy, State Key 
      Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center 
      for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences 
      (NAILS), NJU Institute of AI Biomedicine and Biotechnology, School of Life 
      Sciences, Nanjing University, Nanjing 210023, China.
FAU - Li, Jing
AU  - Li J
AD  - Nanjing DrumTower Hospital Center of Molecular Diagnostic and Therapy, State Key 
      Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center 
      for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences 
      (NAILS), NJU Institute of AI Biomedicine and Biotechnology, School of Life 
      Sciences, Nanjing University, Nanjing 210023, China.
FAU - Zhang, Yujing
AU  - Zhang Y
AD  - Nanjing DrumTower Hospital Center of Molecular Diagnostic and Therapy, State Key 
      Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center 
      for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences 
      (NAILS), NJU Institute of AI Biomedicine and Biotechnology, School of Life 
      Sciences, Nanjing University, Nanjing 210023, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201110
PL  - United States
TA  - Aging (Albany NY)
JT  - Aging
JID - 101508617
RN  - 0 (MIRN222 microRNA, human)
RN  - 0 (MicroRNAs)
SB  - IM
MH  - Adipose Tissue, White/*metabolism
MH  - Animals
MH  - Diabetes Mellitus, Type 2/*blood
MH  - Female
MH  - Gonads/metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - *Insulin Resistance
MH  - Liver/metabolism
MH  - Male
MH  - Mice, Inbred C57BL
MH  - MicroRNAs/*blood
MH  - Muscle, Skeletal/metabolism
MH  - Obesity/*blood
PMC - PMC7746358
OTO - NOTNLM
OT  - adipose
OT  - insulin resistance
OT  - liver
OT  - miR-222
OT  - skeletal muscle
COIS- CONFLICTS OF INTEREST: The authors have declared that no conflicts of interest 
      exist.
EDAT- 2020/11/17 06:00
MHDA- 2021/04/28 06:00
PMCR- 2020/11/30
CRDT- 2020/11/16 20:17
PHST- 2019/09/13 00:00 [received]
PHST- 2020/07/20 00:00 [accepted]
PHST- 2020/11/17 06:00 [pubmed]
PHST- 2021/04/28 06:00 [medline]
PHST- 2020/11/16 20:17 [entrez]
PHST- 2020/11/30 00:00 [pmc-release]
AID - 103891 [pii]
AID - 10.18632/aging.103891 [doi]
PST - ppublish
SO  - Aging (Albany NY). 2020 Nov 10;12(22):22719-22743. doi: 10.18632/aging.103891. 
      Epub 2020 Nov 10.