Effects of high-fat diet and/or body weight on mammary tumor leptin and apoptosis signaling pathways in MMTV-TGF-α mice
Effects of high-fat diet and/or body weight on mammary tumor leptin and apoptosis signaling pathways in MMTV-TGF-α mice
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DOI：
10.1186/bcr1840
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发表时间：
2007-01-01
影响因子：
7.4
通讯作者：
Cleary, Margot P.
中科院分区：
文献类型：
--
作者：
Dogan, Soner;Hu, Xin;Cleary, Margot P.
肥胖是绝经后乳腺癌的危险因素，与饮食诱导肥胖的MMTV-TGF-α小鼠乳腺肿瘤（MT）潜伏期缩短相关。肥胖和乳腺癌之间的一个联系是脂肪因子，瘦素。在这里，重点是饮食诱导的肥胖和MT和乳腺脂肪垫（MFP）瘦素和凋亡信号蛋白。方法MMTV-TGF-α小鼠从10至85周龄喂养低脂或高脂饮食。根据最终体重将高脂肪小鼠分为肥胖倾向组和肥胖抵抗组。结果可触知MT的发生率有显著性差异：肥胖倾向型>肥胖抵抗型>低脂型。与肥胖抵抗和低脂小鼠相比，肥胖倾向小鼠的血清瘦素显著升高。无论体重如何，与高脂肪小鼠相比，低脂肪小鼠具有更高的MFP和MT ObRb（瘦素受体）蛋白和Jak 2（Janus激酶2）蛋白和mRNA水平。瘦素（mRNA）和pSTAT 3（磷酸化的信号转导和转录激活因子3）（mRNA和蛋白质）也更高的低脂肪与高脂肪小鼠的MT。MT和MFP促凋亡蛋白的表达在低脂小鼠中高于高脂小鼠。结论这些结果证实了体重和MT发展之间的联系，体重和血清瘦素水平之间的联系。然而，饮食影响MT和MFP瘦素和凋亡信号蛋白独立于体重。
Introduction Obesity is a risk factor for postmenopausal breast cancer and is associated with shortened mammary tumor (MT) latency in MMTV-TGF-alpha mice with dietary-induced obesity. One link between obesity and breast cancer is the adipokine, leptin. Here, the focus is on diet-induced obesity and MT and mammary fat pad (MFP) leptin and apoptotic signaling proteins.Methods MMTV-TGF-alpha mice were fed low-fat or high-fat diets from 10 to 85 weeks of age. High-Fat mice were divided into Obesity-Prone and Obesity-Resistant groups based on final body weights. Mice were followed to assess MT development and obtain serum, MFP, and MT.Results Incidence of palpable MTs was significantly different: Obesity-Prone > Obesity-Resistant > Low-Fat. Serum leptin was significantly higher in Obesity-Prone compared with Obesity-Resistant and Low-Fat mice. Low-Fat mice had higher MFP and MT ObRb ( leptin receptor) protein and Jak2 (Janus kinase 2) protein and mRNA levels in comparison with High-Fat mice regardless of body weight. Leptin (mRNA) and pSTAT3 (phosphorylated signal transducer and activator of transcription 3) (mRNA and protein) also were higher in MTs from Low-Fat versus High-Fat mice. Expression of MT and MFP pro-apoptotic proteins was higher in Low-Fat versus High-Fat mice.Conclusion These results confirm a connection between body weight and MT development and between body weight and serum leptin levels. However, diet impacts MT and MFP leptin and apoptosis signaling proteins independently of body weight.