Environmental and genetic activation of a brain-adipocyte BDNF/leptin axis causes cancer remission and inhibition.
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.
Cao
Lei
L
Department of Molecular Virology, Immunology and Medical Genetics, and Neuroscience and Neurological Surgery and the Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA. cao.76@osu.edu
Liu
Xianglan
X
Lin
En-Ju D
EJ
Wang
Chuansong
C
Choi
Eugene Y
EY
Riban
Veronique
V
Lin
Benjamin
B
During
Matthew J
MJ
D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D017491:Genes, APC; D006799:Housing, Animal; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism*; D007121:Immunocompetence; D020738:Leptin / Q000378:metabolism*; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009385:Neoplastic Processes; D011897:Random Allocation; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D015398:Signal Transduction; D012931:Social Environment
D019208:Brain-Derived Neurotrophic Factor; D020738:Leptin; D011943:Receptors, Adrenergic, beta