Environmental and Genetic Activation of a Brain-Adipocyte BDNF/Leptin Axis Causes Cancer Remission and Inhibition

被引：287

作者：

Cao, Lei ^{[1
,2
,3
,4
]}

Liu, Xianglan ^{[1
,2
,3
]}

Lin, En-Ju D. ^{[1
,2
,3
]}

Wang, Chuansong ^{[1
,2
,3
]}

Choi, Eugene Y. ^{[1
,2
,3
]}

Riban, Veronique ^{[1
,2
,3
]}

Lin, Benjamin ^{[4
]}

During, Matthew J. ^{[1
,2
,3
,4
,5
]}

机构：

[1] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA

[2] Ohio State Univ, Dept Neurosci & Neurol Surg, Columbus, OH 43210 USA

[3] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA

[4] Cornell Univ, Weill Med Coll, Dept Neurol Surg, New York, NY 10021 USA

[5] Univ Auckland, Ctr Brain Res, Dept Mol Med & Pathol, Fac Med & Hlth Sci, Auckland 1023, New Zealand

来源：

CELL | 2010年 / 142卷 / 01期

基金：

美国国家卫生研究院;

关键词：

NEUROTROPHIC FACTOR; STRESS; LEPTIN; EXERCISE; OBESITY; BDNF; HYPOTHALAMUS; ADAPTATION; PLASTICITY; ENRICHMENT;

D O I：

10.1016/j.cell.2010.05.029

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 brain-derived neurotrophic factor (BDNF) was selectively upregulated by EE, and 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 beta-adrenergic signaling. These results suggest that genetic or environmental activation of this BDNF/leptin axis may have therapeutic significance for cancer.

引用

页码：52 / 64

页数：13

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