PMID- 23779049
OWN - NLM
STAT- MEDLINE
DCOM- 20141124
LR  - 20230216
IS  - 1476-5497 (Electronic)
IS  - 0307-0565 (Print)
IS  - 0307-0565 (Linking)
VI  - 38
IP  - 3
DP  - 2014 Mar
TI  - PPARdelta binding to heme oxygenase 1 promoter prevents angiotensin II-induced 
      adipocyte dysfunction in Goldblatt hypertensive rats.
PG  - 456-65
LID - 10.1038/ijo.2013.116 [doi]
AB  - OBJECTIVE: Renin-angiotensin system (RAS) regulates adipogenic response with 
      adipocyte hypertrophy by increasing oxidative stress. Recent studies have shown 
      the role of peroxisome proliferator-activated receptor-delta (PPARdelta) agonist in 
      attenuation of angiotensin II-induced oxidative stress. The aim of this study was 
      to explore a potential mechanistic link between PPARdelta and the cytoprotective 
      enzyme heme oxygenase-1 (HO-1) and to elucidate the contribution of HO-1 to the 
      adipocyte regulatory effects of PPARdelta agonism in an animal model of enhanced RAS, 
      the Goldblatt 2 kidney 1 clip (2K1C) model. METHOD: We first established a direct 
      stimulatory effect of the PPARdelta agonist (GW 501516) on the HO-1 gene by 
      demonstrating increased luciferase activity in COS-7 cells transfected with a 
      luciferase-HO-1 promoter construct. Sprague-Dawley rats were divided into four 
      groups: sham-operated animals, 2K1C rats and 2K1C rats treated with GW 501516, in 
      the absence or presence of the HO activity inhibitor, stannous mesoporphyrin 
      (SnMP). RESULTS: 2K1C animals had increased visceral adiposity, adipocyte 
      hypertrophy, increased inflammatory cytokines, increased circulatory and adipose 
      tisssue levels of renin and Ang II along with increased adipose tissue gp91 phox 
      expression (P<0.05) when compared with sham-operated animals. Treatment with GW 
      501516 increased adipose tissue HO-1 and adiponectin levels (P<0.01) along with 
      enhancement of Wnt10b and beta-catenin expression. HO-1 induction was accompanied by 
      the decreased expression of Wnt5b, mesoderm specific transcript (mest) and C/EBPalpha 
      levels and an increased number of small adipocytes (P<0.05). These effects of 
      GW501516 were reversed in 2K1C animals exposed to SnMP (P<0.05). CONCLUSION: 
      Taken together, our study demonstrates, for the first time, that increased levels 
      of Ang II contribute towards adipose tissue dysregulation, which is abated by 
      PPARdelta-mediated upregulation of the heme-HO system. These findings highlight the 
      pivotal role and symbiotic relationship of HO-1, adiponectin and PPARdelta in the 
      regulation of metabolic homeostasis in adipose tissues.
FAU - Sodhi, K
AU  - Sodhi K
AD  - Department of Medicine, Joan C Edwards School of Medicine, Marshall University, 
      Huntington, WV, USA.
FAU - Puri, N
AU  - Puri N
AD  - Department of Physiology and Pharmacology, University of Toledo College of 
      Medicine, Toledo, OH, USA.
FAU - Kim, D H
AU  - Kim DH
AD  - Department of Medicine, Joan C Edwards School of Medicine, Marshall University, 
      Huntington, WV, USA.
FAU - Hinds, T D
AU  - Hinds TD
AD  - Department of Physiology and Pharmacology, University of Toledo College of 
      Medicine, Toledo, OH, USA.
FAU - Stechschulte, L A
AU  - Stechschulte LA
AD  - Department of Physiology and Pharmacology, University of Toledo College of 
      Medicine, Toledo, OH, USA.
FAU - Favero, G
AU  - Favero G
AD  - Department of Biomedical Science, Division of Anatomy, University of Brescia, 
      Brescia, Italy.
FAU - Rodella, L
AU  - Rodella L
AD  - Department of Biomedical Science, Division of Anatomy, University of Brescia, 
      Brescia, Italy.
FAU - Shapiro, J I
AU  - Shapiro JI
AD  - Department of Medicine, Joan C Edwards School of Medicine, Marshall University, 
      Huntington, WV, USA.
FAU - Jude, D
AU  - Jude D
AD  - Department of Medicine, Joan C Edwards School of Medicine, Marshall University, 
      Huntington, WV, USA.
FAU - Abraham, N G
AU  - Abraham NG
AD  - Department of Medicine, Joan C Edwards School of Medicine, Marshall University, 
      Huntington, WV, USA.
LA  - eng
GR  - P01 HL034300/HL/NHLBI NIH HHS/United States
GR  - R01 DK056601/DK/NIDDK NIH HHS/United States
GR  - HL-34300/HL/NHLBI NIH HHS/United States
GR  - DK56601/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130619
PL  - England
TA  - Int J Obes (Lond)
JT  - International journal of obesity (2005)
JID - 101256108
RN  - 0 (PPAR delta)
RN  - 11128-99-7 (Angiotensin II)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 3.4.23.15 (Renin)
SB  - IM
MH  - Adipocytes/*metabolism
MH  - Angiotensin II/pharmacology
MH  - Animals
MH  - Enzyme Activation
MH  - Heme Oxygenase-1/*metabolism
MH  - Hypertension, Renovascular/*metabolism
MH  - Kidney/*metabolism
MH  - PPAR delta/*metabolism
MH  - Promoter Regions, Genetic
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Renin/blood
PMC - PMC3950586
EDAT- 2013/06/20 06:00
MHDA- 2014/12/15 06:00
CRDT- 2013/06/20 06:00
PHST- 2012/10/16 00:00 [received]
PHST- 2013/02/20 00:00 [revised]
PHST- 2013/05/29 00:00 [accepted]
PHST- 2013/06/20 06:00 [entrez]
PHST- 2013/06/20 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
AID - ijo2013116 [pii]
AID - 10.1038/ijo.2013.116 [doi]
PST - ppublish
SO  - Int J Obes (Lond). 2014 Mar;38(3):456-65. doi: 10.1038/ijo.2013.116. Epub 2013 
      Jun 19.