Open AccessAdipose VEGF Links the White-to-Brown Fat Switch With Environmental, Genetic, and Pharmacological Stimuli in Male Mice
Author(s) -
Matthew J. During,
Xianglan Liu,
Wei Huang,
Daniel Magee,
Andrew Slater,
Travis McMurphy,
Chuansong Wang,
Lei Cao
Publication year - 2015
Publication title -
endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.674
H-Index - 257
eISSN - 1945-7170
pISSN - 0013-7227
DOI - 10.1210/en.2014-1905
Subject(s) - endocrinology , medicine , adipose tissue , white adipose tissue , biology , vascular endothelial growth factor , brown adipose tissue , adipocyte , receptor , signal transduction , neurotrophic factors , prdm16 , microbiology and biotechnology , vegf receptors
Living in an enriched environment (EE) decreases adiposity, increases energy expenditure, causes resistance to diet induced obesity, and induces brown-like (beige) cells in white fat via activating a hypothalamic-adipocyte axis. Here we report that EE stimulated vascular endothelial growth factor (VEGF) expression in a fat depot-specific manner prior to the emergence of beige cells. The VEGF up-regulation was independent of hypoxia but required intact sympathetic tone to the adipose tissue. Targeted adipose overexpression of VEGF reproduced the browning effect of EE. Adipose-specific VEGF knockout or pharmacological VEGF blockade with antibodies abolished the induction of beige cell by EE. Hypothalamic brain-derived neurotrophic factor stimulated by EE regulated the adipose VEGF expression, and VEGF signaling was essential to the hypothalamic brain-derived neurotrophic factor-induced white adipose tissue browning. Furthermore, VEGF signaling was essential to the beige cells induction by exercise, a β3-adrenergic agonist, and a peroxisome proliferator-activated receptor-γ ligand, suggesting a common downstream pathway integrating diverse upstream mechanisms. Exploiting this pathway may offer potential therapeutic interventions to obesity and metabolic diseases.