PMID- 26812653
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20160127
LR  - 20220809
IS  - 2162-2531 (Print)
IS  - 2162-2531 (Electronic)
IS  - 2162-2531 (Linking)
VI  - 5
IP  - 1
DP  - 2016 Jan 26
TI  - Silencing CCR2 in Macrophages Alleviates Adipose Tissue Inflammation and the 
      Associated Metabolic Syndrome in Dietary Obese Mice.
PG  - e280
LID - 10.1038/mtna.2015.51 [doi]
AB  - Adipose tissue macrophage (ATM)-mediated inflammation is a key feature 
      contributing to the adverse metabolic outcomes of dietary obesity. Recruitment of 
      macrophages to obese adipose tissues (AT) can occur through the engagement of 
      CCR2, the receptor for MCP-1 (monocyte chemoattractant protein-1), which is 
      expressed on peripheral monocytes/macrophages. Here, we show that i.p. 
      administration of a rabies virus glycoprotein-derived acetylcholine 
      receptor-binding peptide effectively delivers complexed siRNA into peritoneal 
      macrophages and ATMs in a mouse model of high-fat diet-induced obesity. Treatment 
      with siRNA against CCR2 inhibited macrophage infiltration and accumulation in AT 
      and, therefore, proinflammatory cytokines produced by macrophages. Consequently, 
      the treatment significantly improved glucose tolerance and insulin sensitivity 
      profiles, and also alleviated the associated symptoms of hepatic steatosis and 
      reduced hepatic triglyceride production. These results demonstrate that 
      disruption of macrophage chemotaxis to the AT through cell-targeted gene 
      knockdown strategies can provide a therapeutic intervention for obesity-related 
      metabolic diseases. The study also highlights a siRNA delivery approach for 
      targeting specific monocyte subsets that contribute to obesity-associated 
      inflammation without affecting the function of other tissue-resident macrophages 
      that are essential for host homeostasis and survival.
FAU - Kim, Jongkil
AU  - Kim J
AD  - Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang 
      University, Seoul, Korea.
FAU - Chung, Kunho
AU  - Chung K
AD  - Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang 
      University, Seoul, Korea.
AD  - Department of Internal Medicine, Section of Infectious Diseases, Yale University 
      School of Medicine, New Haven, Connecticut, USA.
FAU - Choi, Changseon
AU  - Choi C
AD  - Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang 
      University, Seoul, Korea.
AD  - Department of Internal Medicine, Section of Infectious Diseases, Yale University 
      School of Medicine, New Haven, Connecticut, USA.
FAU - Beloor, Jagadish
AU  - Beloor J
AD  - Department of Internal Medicine, Section of Infectious Diseases, Yale University 
      School of Medicine, New Haven, Connecticut, USA.
FAU - Ullah, Irfan
AU  - Ullah I
AD  - Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang 
      University, Seoul, Korea.
FAU - Kim, Nahyeon
AU  - Kim N
AD  - Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang 
      University, Seoul, Korea.
FAU - Lee, Kuen Yong
AU  - Lee KY
AD  - Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang 
      University, Seoul, Korea.
FAU - Lee, Sang-Kyung
AU  - Lee SK
AD  - Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang 
      University, Seoul, Korea.
FAU - Kumar, Priti
AU  - Kumar P
AD  - Department of Internal Medicine, Section of Infectious Diseases, Yale University 
      School of Medicine, New Haven, Connecticut, USA.
LA  - eng
GR  - R01 AI112443/AI/NIAID NIH HHS/United States
PT  - Journal Article
DEP - 20160126
PL  - United States
TA  - Mol Ther Nucleic Acids
JT  - Molecular therapy. Nucleic acids
JID - 101581621
PMC - PMC5012549
EDAT- 2016/01/27 06:00
MHDA- 2016/01/27 06:01
PMCR- 2016/01/01
CRDT- 2016/01/27 06:00
PHST- 2015/06/17 00:00 [received]
PHST- 2015/11/23 00:00 [accepted]
PHST- 2016/01/27 06:00 [entrez]
PHST- 2016/01/27 06:00 [pubmed]
PHST- 2016/01/27 06:01 [medline]
PHST- 2016/01/01 00:00 [pmc-release]
AID - S2162-2531(17)30007-0 [pii]
AID - 10.1038/mtna.2015.51 [doi]
PST - epublish
SO  - Mol Ther Nucleic Acids. 2016 Jan 26;5(1):e280. doi: 10.1038/mtna.2015.51.