Dietary polyphenols suppress elevated levels of proinflammatory mediators and aromatase in the mammary gland of obese mice.

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Subbaramaiah K, Sue E, Bhardwaj P, Du B, Hudis CA, Giri D, Kopelovich L, Zhou XK, Dannenberg AJ

Dietary polyphenols suppress elevated levels of proinflammatory mediators and aromatase in the mammary gland of obese mice.

Cancer Prev Res (Phila). 2013 Sep;6(9):886-97. doi: 10.1158/1940-6207.CAPR-13-0140. Epub 2013 Jul 23.

PubMed ID
23880231 [ View in PubMed
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Abstract

In postmenopausal women, obesity is a risk factor for the development of hormone receptor-positive breast cancer driven by estrogen. After menopause, aromatization of androgen precursors in adipose tissue is a major synthetic source of estrogen. Recently, in mouse models and women, we identified an obesity-inflammation-aromatase axis. This obesity-induced inflammation is characterized by crown-like structures (CLS) consisting of dead adipocytes encircled by macrophages in breast white adipose tissue. CLS occur in association with NF-kappaB activation, elevated levels of proinflammatory mediators, and increased aromatase expression. Saturated fatty acids released from adipocytes have been linked to obesity-related white adipose tissue inflammation. Here we found that stearic acid, a prototypic saturated fatty acid, stimulated Akt-dependent activation of NF-kappaB resulting in increased levels of proinflammatory mediators [TNF-alpha, interleukin (IL)-1beta, COX-2] in macrophages leading, in turn, to the induction of aromatase. Several polyphenols (resveratrol, curcumin, epigallocatechin gallate) blocked these inductive effects of stearic acid. Zyflamend, a widely used polyherbal preparation that contains numerous polyphenols, possessed similar suppressive effects. In a mouse model of obesity, treatment with Zyflamend suppressed levels of phospho-Akt, NF-kappaB binding activity, proinflammatory mediators, and aromatase in the mammary gland. Collectively, these results suggest that targeting the activation of NF-kappaB is a promising approach for reducing levels of proinflammatory mediators and aromatase in inflamed mouse mammary tissue. Further investigation in obese women is warranted.