PMID- 26188090
OWN - NLM
STAT- MEDLINE
DCOM- 20151110
LR  - 20220316
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 464
IP  - 3
DP  - 2015 Aug 28
TI  - Arginase inhibition ameliorates adipose tissue inflammation in mice with 
      diet-induced obesity.
PG  - 840-7
LID - S0006-291X(15)30277-1 [pii]
LID - 10.1016/j.bbrc.2015.07.048 [doi]
AB  - This study examined whether oral administration of an arginase inhibitor 
      regulates adipose tissue macrophage infiltration and inflammation in mice with 
      high fat diet (HFD)-induced obesity. Male C57BL/6 mice (n = 30) were randomly 
      assigned to control (CTL, n = 10), HFD only (n = 10), and HFD with arginase 
      inhibitor N(omega)-hydroxy-nor-l-arginine (HFD with nor-NOHA, n = 10) groups. Plasma 
      and mRNA levels of cytokines in epididymal adipose tissues (EAT), macrophage 
      infiltration into EAT, and macrophage phenotype polarization were measured in the 
      animals after 12 weeks. Additionally, the effects of nor-NOHA on adipose tissue 
      macrophage infiltration and mRNA expression of cytokines were measured in 
      co-cultured 3T3-L1 adipocytes and RAW 264.7 macrophages. Macrophage infiltration 
      into the adipocytes was significantly suppressed by nor-NOHA treatment in 
      adipocyte/macrophage co-culture system and mice with HFD-induced obesity. 
      Pro-inflammatory cytokines, including monocyte chemoattractant protein-1 (MCP-1), 
      tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6), were significantly 
      downregulated, and the anti-inflammatory cytokine IL-10 was significantly 
      upregulated in nor-NOHA-treated co-cultured cells. In the mice with HFD-induced 
      obesity, plasma and mRNA levels of MCP-1 significantly reduced after 
      supplementation with nor-NOHA. In addition, oral supplement of nor-NOHA modified 
      M1/M2 phenotype ratio in the EAT. Oral supplementation of an arginase inhibitor, 
      nor-NOHA, altered M1/M2 macrophage phenotype and macrophage infiltration into 
      HFD-induced obese adipose tissue, thereby improved adipose tissue inflammatory 
      response. These results may indicate that arginase inhibition ameliorates 
      obesity-induced adipose tissue inflammation.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Hu, Huan
AU  - Hu H
AD  - Department of Integrated Biomedical and Life Sciences, Graduate School, Korea 
      University, Seoul 136-701, Republic of Korea.
FAU - Moon, Jiyoung
AU  - Moon J
AD  - Depament of Public Health Sciences, BK21PLUS Program in Embodiment: 
      Health-Society Interaction, Graduate School, Korea University, Seoul 136-701, 
      Republic of Korea.
FAU - Chung, Ji Hyung
AU  - Chung JH
AD  - Department of Applied Bioscience, CHA University, Gyeonggi-do 463-400, Republic 
      of Korea.
FAU - Kim, Oh Yoen
AU  - Kim OY
AD  - Department of Food Science and Nutrition, College of Health Science, Dong-A 
      University, Busan 604-714, Republic of Korea.
FAU - Yu, Rina
AU  - Yu R
AD  - Department of Food Science and Nutrition, University of Ulsan, Ulsan 680-749, 
      Republic of Korea.
FAU - Shin, Min-Jeong
AU  - Shin MJ
AD  - Department of Integrated Biomedical and Life Sciences, Graduate School, Korea 
      University, Seoul 136-701, Republic of Korea; Depament of Public Health Sciences, 
      BK21PLUS Program in Embodiment: Health-Society Interaction, Graduate School, 
      Korea University, Seoul 136-701, Republic of Korea; Korea University Guro 
      Hospital, Korea University, Seoul 152-703, Republic of Korea. Electronic address: 
      mjshin@korea.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150716
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (N(omega)-hydroxynorarginine)
RN  - 94ZLA3W45F (Arginine)
RN  - EC 3.5.3.1 (Arginase)
SB  - IM
MH  - 3T3-L1 Cells/drug effects/metabolism
MH  - Adipocytes/drug effects
MH  - Adipose Tissue/metabolism
MH  - Administration, Oral
MH  - Animals
MH  - Arginase/*antagonists & inhibitors/metabolism
MH  - Arginine/administration & dosage/*analogs & derivatives/pharmacology
MH  - Chemokine CCL2/genetics/metabolism
MH  - Coculture Techniques
MH  - Cytokines/blood/genetics
MH  - Diet, High-Fat/adverse effects
MH  - Enzyme Inhibitors/administration & dosage/*pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - Macrophages/drug effects/metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Obesity/*complications/drug therapy/etiology
MH  - Panniculitis/*drug therapy/etiology
OTO - NOTNLM
OT  - Adipocytes
OT  - Arginase
OT  - Inflammation
OT  - Macrophage infiltration
OT  - Nor-NOHA
EDAT- 2015/07/19 06:00
MHDA- 2015/11/11 06:00
CRDT- 2015/07/19 06:00
PHST- 2015/07/07 00:00 [received]
PHST- 2015/07/08 00:00 [accepted]
PHST- 2015/07/19 06:00 [entrez]
PHST- 2015/07/19 06:00 [pubmed]
PHST- 2015/11/11 06:00 [medline]
AID - S0006-291X(15)30277-1 [pii]
AID - 10.1016/j.bbrc.2015.07.048 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2015 Aug 28;464(3):840-7. doi: 
      10.1016/j.bbrc.2015.07.048. Epub 2015 Jul 16.