Environmental and genetic activation of a brain-adipocyte BDNF/leptin axis causes cancer remission and inhibition.
Environmental and genetic activation of a brain-adipocyte BDNF/leptin axis causes cancer remission and inhibition.
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DOI：
10.1016/j.cell.2010.05.029
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发表时间：
2010-07-09
期刊：
影响因子：
64.5
通讯作者：
During MJ
中科院分区：
文献类型：
--
作者：
Cao L;Liu X;Lin EJ;Wang C;Choi EY;Riban V;Lin B;During MJ
癌症受到其微环境的影响，但更广泛的环境影响也起到了作用，但仍不明确。我们在这里报道，生活在丰富的住房环境中的小鼠显示出肿瘤生长减少和缓解增加。我们在黑色素瘤和结肠癌模型中发现了这种效应，而且它不仅仅是由体力活动引起的。在丰富的环境(EE)中保存的动物的血清在体外抑制癌细胞的增殖，并显著降低瘦素的含量。EE选择性上调下丘脑BDNF，其基因过表达可减轻肿瘤负担，而BDNF基因敲除可阻断EE的作用。从机制上讲，我们发现下丘脑脑源性神经营养因子通过交感神经β-肾上腺素能信号下调脂肪细胞中瘦素的生成。这些结果表明，BDNF/Leptin轴的基因或环境激活可能对癌症具有治疗意义。
Cancer is influenced by its microenvironment, yet broader, environmental effects also play a role but remain poorly defined. We report here that mice living in an enriched housing environment show reduced tumor growth and increased remission. We found this effect in melanoma and colon cancer models, and that it was not caused by physical activity alone. Serum from animals held in an enriched environment (EE) inhibited cancer proliferation in vitro and was markedly lower in leptin. Hypothalamic BDNF was selectively upregulated by EE, its genetic overexpression reduced tumor burden, whereas BDNF knockdown blocked the effect of EE. Mechanistically, we show that hypothalamic BDNF downregulated leptin production in adipocytes via sympathoneural β-adrenergic signaling. These results suggest that genetic or environmental activation of this BDNF/leptin axis may have therapeutic significance for cancer.
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影响因子：
50.5
作者：
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