title: PDGFRβ Regulates Adipose Tissue Expansion and Glucose Metabolism via Vascular Remodeling in Diet-Induced Obesity.
abstract: Platelet-derived growth factor (PDGF) is a key factor in angiogenesis; however, its role in adult obesity remains unclear. In order to clarify its pathophysiological role, we investigated the significance of PDGF receptor β (PDGFRβ) in adipose tissue expansion and glucose metabolism. Mature vessels in the epididymal white adipose tissue (eWAT) were tightly wrapped with pericytes in normal mice. Pericyte desorption from vessels and the subsequent proliferation of endothelial cells were markedly increased in the eWAT of diet-induced obese mice. Analyses with flow cytometry and adipose tissue cultures indicated that PDGF-B caused the detachment of pericytes from vessels in a concentration-dependent manner. M1-macrophages were a major type of cells expressing PDGF-B in obese adipose tissue. In contrast, pericyte detachment was attenuated and vascularity within eWAT was reduced in tamoxifen-inducible conditionalPdgfrb-knockout mice with decreases in adipocyte size and chronic inflammation. Furthermore,Pdgfrb-knockout mice showed enhanced energy expenditure. Consequently, diet-induced obesity and the associated deterioration of glucose metabolism in wild-type mice were absent inPdgfrb-knockout mice. Therefore, PDGF-B-PDGFRβ signaling plays a significant role in the development of adipose tissue neovascularization and appears to be a fundamental target for the prevention of obesity and type 2 diabetes.
authors.affiliation: Department of Clinical Pharmacology, University of Toyama, Toyama, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Onogi
authors.affiliation: Department of Clinical Pharmacology, University of Toyama, Toyama, Japan tsasaoka@pha.u-toyama.ac.jp twada@pha.u-toyama.ac.jp.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Wada
authors.affiliation: Department of Clinical Pharmacology, University of Toyama, Toyama, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Kamiya
authors.affiliation: Department of Clinical Pharmacology, University of Toyama, Toyama, Japan.
authors.forename: Kento
authors.initials: K
authors.lastname: Inata
authors.affiliation: Department of Clinical Pharmacology, University of Toyama, Toyama, Japan.
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Matsuzawa
authors.affiliation: Department of Physiology and Metabolism, Brain/Liver Interface Medicine Research Center, Institute for Frontier Science Initiative, Kanazawa University, Ishikawa, Japan.|Metabolism and Nutrition Research Unit, Innovative Integrated Bio-Research Core, Institute for Frontier Science Initiative, Kanazawa University, Ishikawa, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Inaba
authors.affiliation: Department of Physiology and Metabolism, Brain/Liver Interface Medicine Research Center, Institute for Frontier Science Initiative, Kanazawa University, Ishikawa, Japan.
authors.forename: Kumi
authors.initials: K
authors.lastname: Kimura
authors.affiliation: Department of Physiology and Metabolism, Brain/Liver Interface Medicine Research Center, Institute for Frontier Science Initiative, Kanazawa University, Ishikawa, Japan.|Metabolism and Nutrition Research Unit, Innovative Integrated Bio-Research Core, Institute for Frontier Science Initiative, Kanazawa University, Ishikawa, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inoue
authors.affiliation: Department of Pathology, University of Toyama, Toyama, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Yamamoto
authors.affiliation: Department of Pathology, University of Toyama, Toyama, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ishii
authors.affiliation: Department of Internal Medicine, Kanazawa Medical University, Ishikawa, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Koya
authors.affiliation: Department of Clinical Pharmacology, University of Toyama, Toyama, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsuneki
authors.affiliation: Department of Pathology, University of Toyama, Toyama, Japan.
authors.forename: Masakiyo
authors.initials: M
authors.lastname: Sasahara
authors.affiliation: Department of Clinical Pharmacology, University of Toyama, Toyama, Japan tsasaoka@pha.u-toyama.ac.jp twada@pha.u-toyama.ac.jp.
authors.forename: Toshiyasu
authors.initials: T
authors.lastname: Sasaoka
mesh_terms: D000273:Adipose Tissue / Q000098:blood supply / Q000378:metabolism; D052436:Adipose Tissue, White / Q000098:blood supply / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation / Q000235:genetics*; D059305:Diet, High-Fat; D042783:Endothelial Cells / Q000166:cytology*; D005434:Flow Cytometry; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D008264:Macrophages; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic / Q000235:genetics*; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D020286:Pericytes; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D066253:Vascular Remodeling / Q000235:genetics*
chemical_list: D020574:Proto-Oncogene Proteins c-sis; D020797:Receptor, Platelet-Derived Growth Factor beta; D005947:Glucose