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Diabetes. 2017 Apr;66(4):1008-1021. doi: 10.2337/db16-0881. Epub 2017 Jan 25.

PDGFRβ Regulates Adipose Tissue Expansion and Glucose Metabolism via Vascular Remodeling in Diet-Induced Obesity.

Author information

1
Department of Clinical Pharmacology, University of Toyama, Toyama, Japan.
2
Department of Clinical Pharmacology, University of Toyama, Toyama, Japan tsasaoka@pha.u-toyama.ac.jp twada@pha.u-toyama.ac.jp.
3
Department of Physiology and Metabolism, Brain/Liver Interface Medicine Research Center, Institute for Frontier Science Initiative, Kanazawa University, Ishikawa, Japan.
4
Metabolism and Nutrition Research Unit, Innovative Integrated Bio-Research Core, Institute for Frontier Science Initiative, Kanazawa University, Ishikawa, Japan.
5
Department of Pathology, University of Toyama, Toyama, Japan.
6
Department of Internal Medicine, Kanazawa Medical University, Ishikawa, Japan.

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 conditional Pdgfrb-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 in Pdgfrb-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.

PMID:
28122789
DOI:
10.2337/db16-0881
[Indexed for MEDLINE]
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