title: VEGF-A-Expressing Adipose Tissue Shows Rapid Beiging and Enhanced Survival After Transplantation and Confers IL-4-Independent Metabolic Improvements.
abstract: Adipocyte-derived vascular endothelial growth factor-A (VEGF-A) plays a crucial role in angiogenesis and contributes to adipocyte function and systemic metabolism, such as insulin resistance, chronic inflammation, and beiging of subcutaneous adipose tissue. Using a doxycycline-inducible adipocyte-specific VEGF-A-overexpressing mouse model, we investigated the dynamics of local VEGF-A effects on tissue beiging of adipose tissue transplants. VEGF-A overexpression in adipocytes triggers angiogenesis. We also observed a rapid appearance of beige fat cells in subcutaneous white adipose tissue as early as 2 days postinduction of VEGF-A. In contrast to conventional cold-induced beiging, VEGF-A-induced beiging is independent of interleukin-4. We subjected metabolically healthy VEGF-A-overexpressing adipose tissue to autologous transplantation. Transfer of subcutaneous adipose tissues taken from VEGF-A-overexpressing mice into diet-induced obese mice resulted in systemic metabolic benefits, associated with improved survival of adipocytes and a concomitant reduced inflammatory response. These effects of VEGF-A are tissue autonomous, inducing white adipose tissue beiging and angiogenesis within the transplanted tissue. Our findings indicate that manipulation of adipocyte functions with a bona fide angiogenic factor, such as VEGF-A, significantly improves the survival and volume retention of fat grafts and can convey metabolically favorable properties on the recipient on the basis of beiging.
authors.affiliation: Department of Internal Medicine, Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, TX.|Department of Biological Sciences, School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, South Korea.
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, TX.|National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Inje University, and Cardiovascular and Metabolic Disease Center, Inje University, Busanjin-gu, Busan, South Korea.
authors.forename: Min
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, TX.|Center for Metabolic and Degenerative Diseases, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center at Houston, Houston, TX.
authors.forename: Kai
authors.initials: K
authors.lastname: Sun
authors.affiliation: Department of Internal Medicine, Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Yu Aaron
authors.initials: YA
authors.lastname: An
authors.affiliation: Center for Metabolic and Degenerative Diseases, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center at Houston, Houston, TX.
authors.forename: Xue
authors.initials: X
authors.lastname: Gu
authors.affiliation: Department of Internal Medicine, Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, TX philipp.scherer@utsouthwestern.edu.|Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Philipp E
authors.initials: PE
authors.lastname: Scherer
mesh_terms: D000069797:Adipocytes, Beige / Q000166:cytology / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism / Q000637:transplantation; D000069796:Adipose Tissue, Beige / Q000098:blood supply / Q000166:cytology / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000098:blood supply / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology; D005455:Fluorescent Antibody Technique; D005951:Glucose Tolerance Test; D015847:Interleukin-4 / Q000276:immunology; D051379:Mice; D018919:Neovascularization, Physiologic / Q000235:genetics*; D009765:Obesity / Q000235:genetics*; D016133:Polymerase Chain Reaction; D050151:Subcutaneous Fat / Q000098:blood supply / Q000166:cytology / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D015847:Interleukin-4