Caloric restriction reverses obesity-induced mammary gland inflammation in mice.
Caloric restriction reverses obesity-induced mammary gland inflammation in mice.
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DOI：
10.1158/1940-6207.capr-12-0467
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发表时间：
2013-04
期刊：
影响因子：
--
通讯作者：
Dannenberg AJ
中科院分区：
文献类型：
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作者：
Bhardwaj P;Du B;Zhou XK;Sue E;Harbus MD;Falcone DJ;Giri D;Hudis CA;Kopelovich L;Subbaramaiah K;Dannenberg AJ
肥胖是绝经后妇女发生激素受体阳性乳腺癌的危险因素。雌激素的合成由芳香化酶催化。最近，我们在小鼠模型和女性中发现了肥胖-炎症-芳香化酶轴。在肥胖小鼠模型中，在乳腺（MG）中发现了以冠状结构（CLS）为特征的炎性病灶，该冠状结构由被巨噬细胞包围的死亡脂肪细胞组成。超重和肥胖妇女乳腺CLS发生率最高。CLS与脂肪细胞肥大、NF-κB活化、促炎介质和芳香化酶水平升高以及孕酮受体（PR）表达增加相关。总的来说，这些发现为肥胖、慢性炎症和绝经后乳腺癌之间的联系提供了合理的解释。在这里，我们研究了热量限制（CR）是否逆转了肥胖小鼠MG的炎症状态和相关分子的变化。将切除卵巢的肥胖C57 BL/6 J小鼠进行30%CR 7或14周。将CR小鼠中的发现与随意喂食高脂肪饮食的小鼠或喂食低脂饮食的对照小鼠中的结果进行比较。CR与乳房CLS/cm 2下降超过75%相关。CR后组织学炎症的减少与脂肪细胞直径和MCP-1水平的降低、NF-κB结合活性的降低以及促炎介质、芳香化酶和PR水平的正常化相关。总之，肥胖相关的MG炎症以及芳香化酶和PR水平的升高在CR后被逆转。我们的研究结果为确定减肥是否可以逆转女性肥胖相关的乳腺炎症提供了依据。
Obesity is a risk factor for the development of hormone receptor-positive breast cancer in post-menopausal 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 (MG). 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 post-menopausal breast cancer. Here we investigated whether caloric restriction (CR) reversed the inflammatory state and related molecular changes in the MG 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 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 histological inflammation following CR was associated with decreased adipocyte diameter and 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 MG 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.