PMID- 29222347
OWN - NLM
STAT- MEDLINE
DCOM- 20190610
LR  - 20200723
IS  - 1940-6215 (Electronic)
IS  - 1940-6207 (Print)
IS  - 1940-6215 (Linking)
VI  - 11
IP  - 4
DP  - 2018 Apr
TI  - Pioglitazone Inhibits Periprostatic White Adipose Tissue Inflammation in Obese 
      Mice.
PG  - 215-226
LID - 10.1158/1940-6207.CAPR-17-0296 [doi]
AB  - Obesity is associated with an increased incidence of high-grade prostate cancer 
      and poor prognosis for prostate cancer patients. Recently, we showed that 
      obesity-related periprostatic white adipose tissue (WAT) inflammation, 
      characterized by crown-like structures (CLS) consisting of dead or dying 
      adipocytes surrounded by macrophages, was associated with high-grade prostate 
      cancer. It is possible, therefore, that agents that suppress periprostatic WAT 
      inflammation will alter the development or progression of prostate cancer. 
      Pioglitazone, a ligand of PPARgamma, is used to treat diabetes and possesses 
      anti-inflammatory properties. Here, our main objectives were to determine whether 
      pioglitazone inhibited obesity-related periprostatic WAT inflammation in mice and 
      then to elucidate the underlying mechanism. Treatment with pioglitazone reduced 
      the density of CLS in periprostatic fat and suppressed levels of TNFalpha, TGFbeta, and 
      the chemokine monocyte chemoattractant protein-1 (MCP-1). Importantly, the 
      ability of pioglitazone to suppress periprostatic WAT inflammation was abrogated 
      in MCP-1 knockout mice. Pioglitazone caused dose-dependent induction of both 
      adiponectin, an anti-inflammatory adipokine, and its receptor AdipoR2 in cultured 
      3T3-L1 cells and in periprostatic WAT of obese mice. Pioglitazone blocked 
      TNFalpha-mediated induction of MCP-1 in 3T3-L1 cells, an effect that was attenuated 
      when either adiponectin or AdipoR2 were silenced. Taken together, 
      pioglitazone-mediated induction of adiponectin suppressed the elevation in MCP-1 
      levels, thereby attenuating obesity-related periprostatic WAT inflammation. These 
      findings strengthen the rationale for future efforts to determine whether 
      targeting the PPARgamma-adiponectin-MCP-1 axis will decrease periprostatic adipose 
      inflammation and thereby reduce the risk of high-grade prostate cancer or improve 
      outcomes for men with prostate cancer. Cancer Prev Res; 11(4); 215-26. (c)2017 
      AACR.
CI  - (c)2017 American Association for Cancer Research.
FAU - Miyazawa, Miki
AU  - Miyazawa M
AD  - Department of Medicine, Weill Cornell Medical College, New York, New York.
FAU - Subbaramaiah, Kotha
AU  - Subbaramaiah K
AD  - Department of Medicine, Weill Cornell Medical College, New York, New York.
FAU - Bhardwaj, Priya
AU  - Bhardwaj P
AD  - Department of Medicine, Weill Cornell Medical College, New York, New York.
FAU - Zhou, Xi Kathy
AU  - Zhou XK
AD  - Department of Healthcare Policy and Research, Weill Cornell Medical College, New 
      York, New York.
FAU - Wang, Hanhan
AU  - Wang H
AD  - Department of Healthcare Policy and Research, Weill Cornell Medical College, New 
      York, New York.
FAU - Falcone, Domenick J
AU  - Falcone DJ
AD  - Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, 
      New York, New York.
FAU - Giri, Dilip D
AU  - Giri DD
AD  - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New 
      York.
FAU - Dannenberg, Andrew J
AU  - Dannenberg AJ
AD  - Department of Medicine, Weill Cornell Medical College, New York, New York. 
      ajdannen@med.cornell.edu.
LA  - eng
GR  - P30 CA008748/CA/NCI NIH HHS/United States
GR  - P50 CA092629/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20171208
PL  - United States
TA  - Cancer Prev Res (Phila)
JT  - Cancer prevention research (Philadelphia, Pa.)
JID - 101479409
RN  - 0 (Chemokine CCL2)
RN  - 0 (Hypoglycemic Agents)
RN  - X4OV71U42S (Pioglitazone)
SB  - IM
MH  - Adipose Tissue, White/*drug effects/immunology/metabolism/pathology
MH  - Animals
MH  - Cells, Cultured
MH  - Chemokine CCL2/*physiology
MH  - Diet, High-Fat/adverse effects
MH  - Hypoglycemic Agents/*pharmacology
MH  - Inflammation/*drug therapy/etiology/metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Obese
MH  - Pioglitazone/*pharmacology
MH  - Prostate/*drug effects/immunology/metabolism/pathology
PMC - PMC5882568
MID - NIHMS926475
COIS- Disclosures: None of the authors disclosed potential conflicts of interest.
EDAT- 2017/12/10 06:00
MHDA- 2019/06/14 06:00
PMCR- 2019/04/01
CRDT- 2017/12/10 06:00
PHST- 2017/09/15 00:00 [received]
PHST- 2017/10/27 00:00 [revised]
PHST- 2017/12/01 00:00 [accepted]
PHST- 2017/12/10 06:00 [pubmed]
PHST- 2019/06/14 06:00 [medline]
PHST- 2017/12/10 06:00 [entrez]
PHST- 2019/04/01 00:00 [pmc-release]
AID - 1940-6207.CAPR-17-0296 [pii]
AID - 10.1158/1940-6207.CAPR-17-0296 [doi]
PST - ppublish
SO  - Cancer Prev Res (Phila). 2018 Apr;11(4):215-226. doi: 
      10.1158/1940-6207.CAPR-17-0296. Epub 2017 Dec 8.