Caloric restriction reverses obesity-induced mammary gland inflammation in mice

Priya Bhardwaj, Baoheng Du, Xi Kathy Zhou, Erika Sue, Michael D. Harbus, Domenick J. Falcone, Dilip Giri, Clifford A. Hudis, Levy Kopelovich, Kotha Subbaramaiah, Andrew J. Dannenberg

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

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-κB, 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/cm2. Reduced histologic inflammation following CR was associated with decreased adipocyte diameter and monocyte chemoattractant protein-1 (MCP-1) levels, reduced NF-κB 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.

Original languageEnglish (US)
Pages (from-to)282-289
Number of pages8
JournalCancer Prevention Research
Volume6
Issue number4
DOIs
StatePublished - Apr 2013

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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