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Publication : Environmental and genetic activation of a brain-adipocyte BDNF/leptin axis causes cancer remission and inhibition.

First Author  Cao L Year  2010
Journal  Cell Volume  142
Issue  1 Pages  52-64
PubMed ID  20603014 Mgi Jnum  J:167939
Mgi Id  MGI:4881383 Doi  10.1016/j.cell.2010.05.029
Citation  Cao L, et al. (2010) Environmental and genetic activation of a brain-adipocyte BDNF/leptin axis causes cancer remission and inhibition. Cell 142(1):52-64
abstractText  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.
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