title: Adipose VEGF Links the White-to-Brown Fat Switch With Environmental, Genetic, and Pharmacological Stimuli in Male Mice.
abstract: 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.
authors.affiliation: Department of Molecular Virology, Immunology, and Medical Genetics and The Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: During
authors.forename: Xianglan
authors.initials: X
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Daniel
authors.initials: D
authors.lastname: Magee
authors.forename: Andrew
authors.initials: A
authors.lastname: Slater
authors.forename: Travis
authors.initials: T
authors.lastname: McMurphy
authors.forename: Chuansong
authors.initials: C
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Cao
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D042461:Vascular Endothelial Growth Factor A