PMID- 33450179
OWN - NLM
STAT- MEDLINE
DCOM- 20220125
LR  - 20220408
IS  - 1932-7420 (Electronic)
IS  - 1550-4131 (Print)
IS  - 1550-4131 (Linking)
VI  - 33
IP  - 4
DP  - 2021 Apr 6
TI  - MiR-690, an exosomal-derived miRNA from M2-polarized macrophages, improves 
      insulin sensitivity in obese mice.
PG  - 781-790.e5
LID - S1550-4131(20)30717-8 [pii]
LID - 10.1016/j.cmet.2020.12.019 [doi]
AB  - Insulin resistance is a major pathophysiologic defect in type 2 diabetes and 
      obesity, while anti-inflammatory M2-like macrophages are important in maintaining 
      normal metabolic homeostasis. Here, we show that M2 polarized bone marrow-derived 
      macrophages (BMDMs) secrete miRNA-containing exosomes (Exos), which improve 
      glucose tolerance and insulin sensitivity when given to obese mice. Depletion of 
      their miRNA cargo blocks the ability of M2 BMDM Exos to enhance insulin 
      sensitivity. We found that miR-690 is highly expressed in M2 BMDM Exos and 
      functions as an insulin sensitizer both in vivo and in vitro. Expressing an 
      miR-690 mimic in miRNA-depleted BMDMs generates Exos that recapitulate the 
      effects of M2 BMDM Exos on metabolic phenotypes. Nadk is a bona fide target mRNA 
      of miR-690, and Nadk plays a role in modulating macrophage inflammation and 
      insulin signaling. Taken together, these data suggest miR-690 could be a new 
      therapeutic insulin-sensitizing agent for metabolic disease.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Ying, Wei
AU  - Ying W
AD  - Division of Endocrinology & Metabolism, Department of Medicine, University of 
      California, San Diego, San Diego, CA, USA. Electronic address: 
      weying@health.ucsd.edu.
FAU - Gao, Hong
AU  - Gao H
AD  - Division of Endocrinology & Metabolism, Department of Medicine, University of 
      California, San Diego, San Diego, CA, USA.
FAU - Dos Reis, Felipe Castellani Gomes
AU  - Dos Reis FCG
AD  - Division of Endocrinology & Metabolism, Department of Medicine, University of 
      California, San Diego, San Diego, CA, USA.
FAU - Bandyopadhyay, Gautam
AU  - Bandyopadhyay G
AD  - Division of Endocrinology & Metabolism, Department of Medicine, University of 
      California, San Diego, San Diego, CA, USA.
FAU - Ofrecio, Jachelle M
AU  - Ofrecio JM
AD  - Division of Endocrinology & Metabolism, Department of Medicine, University of 
      California, San Diego, San Diego, CA, USA.
FAU - Luo, Zhenlong
AU  - Luo Z
AD  - Division of Endocrinology & Metabolism, Department of Medicine, University of 
      California, San Diego, San Diego, CA, USA.
FAU - Ji, Yudong
AU  - Ji Y
AD  - Division of Endocrinology & Metabolism, Department of Medicine, University of 
      California, San Diego, San Diego, CA, USA.
FAU - Jin, Zhongmou
AU  - Jin Z
AD  - Division of Biological Sciences, University of California, San Diego, San Diego, 
      CA, USA.
FAU - Ly, Crystal
AU  - Ly C
AD  - Division of Biological Sciences, University of California, San Diego, San Diego, 
      CA, USA.
FAU - Olefsky, Jerrold M
AU  - Olefsky JM
AD  - Division of Endocrinology & Metabolism, Department of Medicine, University of 
      California, San Diego, San Diego, CA, USA. Electronic address: 
      jolefsky@health.ucsd.edu.
LA  - eng
GR  - P30 DK063491/DK/NIDDK NIH HHS/United States
GR  - R00 DK115998/DK/NIDDK NIH HHS/United States
GR  - R01 DK101395/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20210114
PL  - United States
TA  - Cell Metab
JT  - Cell metabolism
JID - 101233170
RN  - 0 (Antagomirs)
RN  - 0 (Insulin)
RN  - 0 (MIRN690 microRNA, mouse)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Small Interfering)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.1.23 (NAD kinase)
RN  - EC 3.1.26.3 (Dicer1 protein, mouse)
RN  - EC 3.1.26.3 (Ribonuclease III)
RN  - EC 3.6.4.13 (DEAD-box RNA Helicases)
SB  - IM
CIN - Nat Rev Endocrinol. 2021 Apr;17(4):192. PMID: 33526905
CIN - Cell Metab. 2021 Apr 6;33(4):700-702. PMID: 33826911
MH  - Adipocytes/cytology/metabolism
MH  - Animals
MH  - Antagomirs/metabolism
MH  - DEAD-box RNA Helicases/deficiency/genetics
MH  - Diet, High-Fat
MH  - Exosomes/*metabolism
MH  - Hepatocytes/cytology/metabolism
MH  - Insulin/metabolism
MH  - Insulin Resistance
MH  - Macrophages/cytology/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Obese
MH  - MicroRNAs/antagonists & inhibitors/genetics/*metabolism
MH  - Muscle Fibers, Skeletal/cytology/metabolism
MH  - Obesity/metabolism/pathology
MH  - Phosphotransferases (Alcohol Group Acceptor)/antagonists & 
      inhibitors/genetics/metabolism
MH  - RNA Interference
MH  - RNA, Small Interfering/metabolism
MH  - Ribonuclease III/deficiency/genetics
PMC - PMC8035248
MID - NIHMS1663092
OTO - NOTNLM
OT  - exosomes
OT  - insulin sensitivity
OT  - macrophages
OT  - miR-690
OT  - obesity
COIS- Declaration of interests W.Y. and J.M. Olefsky are co-inventors on a provisional 
      patent covering the use of miR-690 as an insulin sensitizer. Outside of this 
      there are no competing interests for any of the authors.
EDAT- 2021/01/16 06:00
MHDA- 2022/01/27 06:00
PMCR- 2022/04/06
CRDT- 2021/01/15 20:08
PHST- 2020/08/10 00:00 [received]
PHST- 2020/10/20 00:00 [revised]
PHST- 2020/12/28 00:00 [accepted]
PHST- 2021/01/16 06:00 [pubmed]
PHST- 2022/01/27 06:00 [medline]
PHST- 2021/01/15 20:08 [entrez]
PHST- 2022/04/06 00:00 [pmc-release]
AID - S1550-4131(20)30717-8 [pii]
AID - 10.1016/j.cmet.2020.12.019 [doi]
PST - ppublish
SO  - Cell Metab. 2021 Apr 6;33(4):781-790.e5. doi: 10.1016/j.cmet.2020.12.019. Epub 
      2021 Jan 14.