PMID- 23430756
OWN - NLM
STAT- MEDLINE
DCOM- 20131021
LR  - 20230922
IS  - 1940-6215 (Electronic)
IS  - 1940-6207 (Print)
IS  - 1940-6215 (Linking)
VI  - 6
IP  - 4
DP  - 2013 Apr
TI  - Caloric restriction reverses obesity-induced mammary gland inflammation in mice.
PG  - 282-9
LID - 10.1158/1940-6207.CAPR-12-0467 [doi]
AB  - Obesity is a risk factor for the development of hormone receptor-positive breast 
      cancer in postmenopausal women. Estrogen synthesis is catalyzed by aromatase. 
      Recently, we identified an obesity-->inflammation-->aromatase axis in mouse models 
      and women. In mouse models of obesity, inflammatory foci characterized by 
      crown-like structures (CLS) consisting of dead adipocytes encircled by 
      macrophages were found in the mammary gland. CLS of the breast were found in most 
      overweight and obese women. CLS were associated with adipocyte hypertrophy, 
      activation of NF-kappaB, elevated levels of proinflammatory mediators and aromatase, 
      and increased expression of the progesterone receptor (PR). Collectively, these 
      findings provide a plausible explanation for the link between obesity, chronic 
      inflammation, and postmenopausal breast cancer. Here, we investigated whether 
      caloric restriction (CR) reversed the inflammatory state and related molecular 
      changes in the mammary gland of obese mice. Obese ovariectomized C57BL/6J mice 
      were subjected to 30% CR for 7 or 14 weeks. Findings in CR mice were compared 
      with the results in mice fed a high-fat diet ad libitum or with control mice fed 
      a low-fat diet. CR was associated with more than a 75% decrease in mammary 
      CLS/cm(2). Reduced histologic inflammation following CR was associated with 
      decreased adipocyte diameter and monocyte chemoattractant protein-1 (MCP-1) 
      levels, reduced NF-kappaB binding activity, and normalization of levels of 
      proinflammatory mediators, aromatase, and PR. In summary, obesity-related 
      inflammation of the mammary gland and elevated aromatase and PR levels were 
      reversed with CR. Our results provide a rationale for determining whether weight 
      loss can reverse breast inflammation associated with obesity in women.
FAU - Bhardwaj, Priya
AU  - Bhardwaj P
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
FAU - Du, Baoheng
AU  - Du B
FAU - Zhou, Xi Kathy
AU  - Zhou XK
FAU - Sue, Erika
AU  - Sue E
FAU - Harbus, Michael D
AU  - Harbus MD
FAU - Falcone, Domenick J
AU  - Falcone DJ
FAU - Giri, Dilip
AU  - Giri D
FAU - Hudis, Clifford A
AU  - Hudis CA
FAU - Kopelovich, Levy
AU  - Kopelovich L
FAU - Subbaramaiah, Kotha
AU  - Subbaramaiah K
FAU - Dannenberg, Andrew J
AU  - Dannenberg AJ
LA  - eng
GR  - R01 CA154481/CA/NCI NIH HHS/United States
GR  - 1R01CA154481/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Retracted Publication
DEP - 20130219
PL  - United States
TA  - Cancer Prev Res (Phila)
JT  - Cancer prevention research (Philadelphia, Pa.)
JID - 101479409
RN  - 0 (Inflammation Mediators)
RN  - 0 (Receptors, Progesterone)
RN  - EC 1.14.14.1 (Aromatase)
SB  - IM
RIN - Cancer Prev Res (Phila). 2022 Jun 2;15(6):410. PMID: 35652226
CIN - Fed Regist. 2023 Sep 13;88(176):62800-62803. PMID: 37736072
CIN - Fed Regist. 2023 Sep 13;88(176):62803-62807. PMID: 37736073
MH  - Animals
MH  - Aromatase/genetics/metabolism
MH  - *Caloric Restriction
MH  - Disease Models, Animal
MH  - Female
MH  - Inflammation Mediators/metabolism
MH  - Mammary Glands, Animal/metabolism/pathology
MH  - Mastitis/*diet therapy/*etiology/metabolism/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Obesity/*complications/*diet therapy/genetics/metabolism
MH  - Receptors, Progesterone/genetics/metabolism
MH  - Weight Gain/immunology
PMC - PMC3618560
MID - NIHMS446444
EDAT- 2013/02/23 06:00
MHDA- 2013/10/22 06:00
PMCR- 2014/04/01
CRDT- 2013/02/23 06:00
PHST- 2013/02/23 06:00 [entrez]
PHST- 2013/02/23 06:00 [pubmed]
PHST- 2013/10/22 06:00 [medline]
PHST- 2014/04/01 00:00 [pmc-release]
AID - 1940-6207.CAPR-12-0467 [pii]
AID - 10.1158/1940-6207.CAPR-12-0467 [doi]
PST - ppublish
SO  - Cancer Prev Res (Phila). 2013 Apr;6(4):282-9. doi: 
      10.1158/1940-6207.CAPR-12-0467. Epub 2013 Feb 19.