PMID- 25551221
OWN - NLM
STAT- MEDLINE
DCOM- 20160504
LR  - 20220409
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 12
DP  - 2014
TI  - Angiotensin II receptor blocker ameliorates stress-induced adipose tissue 
      inflammation and insulin resistance.
PG  - e116163
LID - 10.1371/journal.pone.0116163 [doi]
LID - e116163
AB  - A strong causal link exists between psychological stress and insulin resistance 
      as well with hypertension. Meanwhile, stress-related responses play critical 
      roles in glucose metabolism in hypertensive patients. As clinical trials suggest 
      that angiotensin-receptor blocker delays the onset of diabetes in hypertensive 
      patients, we investigated the effects of irbesartan on stress-induced adipose 
      tissue inflammation and insulin resistance. C57BL/6J mice were subjected to 
      2-week intermittent restraint stress and orally treated with vehicle, 3 and 10 
      mg/kg/day irbesartan. The plasma concentrations of lipid and proinflammatory 
      cytokines [Monocyte Chemoattractant Protein-1 (MCP-1), tumor necrosis factor-alpha, 
      and interleukin-6] were assessed with enzyme-linked immunosorbent assay. 
      Monocyte/macrophage accumulation in inguinal white adipose tissue (WAT) was 
      observed with CD11b-positive cell counts and mRNA expressions of CD68 and F4/80 
      using immunohistochemistry and RT-PCR methods respectively. The mRNA levels of 
      angiotensinogen, proinflammatory cytokines shown above, and adiponectin in WAT 
      were also assessed with RT-PCR method. Glucose metabolism was assessed by glucose 
      tolerance tests (GTTs) and insulin tolerance tests, and mRNA expression of 
      insulin receptor substrate-1 (IRS-1) and glucose transporter 4 (GLUT4) in WAT. 
      Restraint stress increased monocyte accumulation, plasma free fatty acids, 
      expression of angiotensinogen and proinflammatory cytokines including MCP-1, and 
      reduced adiponectin. Irbesartan reduced stress-induced monocyte accumulation in 
      WAT in a dose dependent manner. Irbesartan treatment also suppressed induction of 
      adipose angiotensinogen and proinflammatory cytokines in WAT and blood, and 
      reversed changes in adiponectin expression. Notably, irbesartan suppressed 
      stress-induced reduction in adipose tissue weight and free fatty acid release, 
      and improved insulin tolerance with restoration of IRS-1 and GLUT4 mRNA 
      expressions in WAT. The results indicate that irbesartan improves stress-induced 
      adipose tissue inflammation and insulin resistance. Our results suggests that 
      irbesartan treatment exerts additive benefits for glucose metabolism in 
      hypertensive patients with mental stress.
FAU - Hayashi, Motoharu
AU  - Hayashi M
AD  - Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, 
      Japan.
FAU - Takeshita, Kyosuke
AU  - Takeshita K
AD  - Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, 
      Japan; Department of Clinical Laboratory, Nagoya University Hospital, Nagoya, 
      Japan.
FAU - Uchida, Yasuhiro
AU  - Uchida Y
AD  - Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, 
      Japan.
FAU - Yamamoto, Koji
AU  - Yamamoto K
AD  - Department of Blood Transfusion, Nagoya University Hospital, Nagoya, Japan.
FAU - Kikuchi, Ryosuke
AU  - Kikuchi R
AD  - Department of Clinical Laboratory, Nagoya University Hospital, Nagoya, Japan.
FAU - Nakayama, Takayuki
AU  - Nakayama T
AD  - Department of Blood Transfusion, Aichi Medical University Hospital, Nagakute, 
      Japan.
FAU - Nomura, Emiko
AU  - Nomura E
AD  - Department of Blood Transfusion, Nagoya University Hospital, Nagoya, Japan.
FAU - Cheng, Xian Wu
AU  - Cheng XW
AD  - Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, 
      Japan.
FAU - Matsushita, Tadashi
AU  - Matsushita T
AD  - Department of Blood Transfusion, Nagoya University Hospital, Nagoya, Japan.
FAU - Nakamura, Shigeo
AU  - Nakamura S
AD  - Department of Pathology, Nagoya University Hospital, Nagoya, Japan.
FAU - Murohara, Toyoaki
AU  - Murohara T
AD  - Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, 
      Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141231
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Adipokines)
RN  - 0 (Angiotensin II Type 1 Receptor Blockers)
RN  - 0 (Biphenyl Compounds)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Tetrazoles)
RN  - 11002-13-4 (Angiotensinogen)
RN  - J0E2756Z7N (Irbesartan)
SB  - IM
MH  - Adipokines/genetics
MH  - Adipose Tissue, White/drug effects/metabolism
MH  - Angiotensin II Type 1 Receptor Blockers/*pharmacology
MH  - Angiotensinogen/genetics
MH  - Animals
MH  - Biphenyl Compounds/*pharmacology
MH  - Chemokine CCL2/blood
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - *Insulin Resistance/physiology
MH  - Irbesartan
MH  - Lipolysis/drug effects
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Panniculitis/*drug therapy/etiology/metabolism
MH  - Stress, Physiological
MH  - Tetrazoles/*pharmacology
PMC - PMC4281136
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/01/01 06:00
MHDA- 2016/05/05 06:00
PMCR- 2014/12/31
CRDT- 2015/01/01 06:00
PHST- 2014/06/26 00:00 [received]
PHST- 2014/12/03 00:00 [accepted]
PHST- 2015/01/01 06:00 [entrez]
PHST- 2015/01/01 06:00 [pubmed]
PHST- 2016/05/05 06:00 [medline]
PHST- 2014/12/31 00:00 [pmc-release]
AID - PONE-D-14-28550 [pii]
AID - 10.1371/journal.pone.0116163 [doi]
PST - epublish
SO  - PLoS One. 2014 Dec 31;9(12):e116163. doi: 10.1371/journal.pone.0116163. 
      eCollection 2014.