Transplantation of Normal Adipose Tissue Improves Blood Flow and Reduces Inflammation in High Fat Fed Mice With Hindlimb Ischemia.

Liyuan Chen,Yulin Luo,Rong Li,Jianbo Wu,Jing He,Liqun Wuang,Yaofang Liu,Yongjie Li,Ningbo Pang,Lin Wang,Ni Chen,Liping Zhang

doi:10.3389/fphys.2018.00197

Abstract

Background: Fat deposition is associated with peripheral arterial disease. Adipose tissue has recently been implicated in vascular remodeling and angiogenic activity. We hypothesized that the transplantation of adipose tissues from normal mice improves blood flow perfusion and neovascularization in high-fat diet fed mice.Methods: After 14 weeks of high-fat diet (HFD)-fed mice, unilateral hind limb ischemia was performed. Subcutaneous white adipose tissue (WAT) and brown adipose tissue (BAT) fat pads were harvested from normal EGFP mice, and subcutaneously transplanted over the region of the adductor muscles of HFD mice. Blood flow was measured using Laser Doppler Scanner. Vascular density, macrophages infiltration, and macrophage polarization were examined by RT-qPCR, and immunohistochemistry.Results: We found that the transplantation of WAT derived from normal mice improved functional blood flow in HFD-fed mice compared to mice transplanted with BAT and sham-treated mice. WAT transplantation increased the recruitment of pericytes associated with nascent blood vessels, but did not affect capillary formation. Furthermore, transplantation of WAT ameliorated HFD-induced insulin resistance, M2 macrophage predominance and the release of arteriogenic factors in ischemic muscles. Mice receiving WAT also displayed a marked reduction in several proinflammatory cytokines. In contrast, mice transplanted with BAT were glucose intolerant and demonstrated increased IL-6 levels in ischemic muscles.Conclusion: These results indicate that transplantation of adipose tissue elicits improvements in blood perfusion and beneficial effects on systemic glucose homeostasis and could be a promising therapeutic option for the treatment of diabetic peripheral arterial disease.

Highlights

The distribution of adipose tissue plays a fundamental role in the prevalence of obesity-related comorbidities
To examine the role of adipose tissues in reversing blood perfusion in highfat diet (HFD) mice, we introduced wild-type fat by surgical implantation
At 21 days after transplantation, the grafts had a healthy gross and morphological appearance that was visible by fluorescent imaging (Figures 1A–C). enhanced Green Fluorescent Protein (eGFP) expressing cells were observed in the sections of ischemic adductor muscles in both WAT and BAT transplanted mice (Supplemental Figure 1)

Summary

Introduction

The distribution of adipose tissue plays a fundamental role in the prevalence of obesity-related comorbidities. Adipose tissue macrophages could be potential mediators of the formation of collateral circulation Transplantation of both white and brown adipose tissue produces different beneficial effects associated with the regulation of glucose homeostasis and insulin sensitivity (Thomou et al, 2007; Tran et al, 2008). Min et al (2016) demonstrated the potential of capillary progenitors to cure obesity-associated disturbances in glucose homeostasis ATMs consist of two different phenotypes Periadventitial fat has been primarily considered to act as a structural support for blood vessels It is unclear whether adipose tissue cellular remodeling related to chronic inflammation and vascular alterations may compromise surrounding blood vessel function and negatively affect glucose homeostasis in peripherally ischemic type 2 diabetic mice. We hypothesized that the transplantation of adipose tissues from normal mice improves blood flow perfusion and neovascularization in high-fat diet fed mice

Methods

Results

Conclusion