Obese adipose tissue remodeling, malfunctioning, and chronic inflammation visualized by in vivo molecular imaging

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  • Nishimura Satoshi
    Department of Cardiovascular Medicine, The University of Tokyo PRESTO, Japan Science and Technology Agency Nano-Bioengineering Education Program, The University of Tokyo
  • Nagasaki Mika
    Department of Cardiovascular Medicine, The University of Tokyo Computational Diagnostic Radiology and Preventive Medicine, The University of Tokyo
  • Manabe Ichiro
    Department of Cardiovascular Medicine, The University of Tokyo PRESTO, Japan Science and Technology Agency Nano-Bioengineering Education Program, The University of Tokyo
  • Kadowaki Takashi
    Department of Metabolic Diseases, The University of Tokyo
  • Nagai Ryozo
    Department of Cardiovascular Medicine, The University of Tokyo

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Abstract

Metabolic syndrome is a major risk factor of cardiovascular events, and obese visceral adipose tissue remodeling and malfunctioning based on chronic inflammation play a central role. To assess dynamic multi-cellular interplay, a novel ex vivo and in vivo adipose tissue imaging method was developed. We found close spatial and temporal interrelationships between angiogenesis and adipogenesis, and both were augmented in obese adipose. In addition, we found increased leukocyte-platelet-endothelial cell interactions in the microcirculation of obese visceral adipose that were indicative of activation of the leukocyte adhesion cascade, a hallmark of inflammation. Both macrophages and endothelial cells showed increased adhesion molecules, and platelets were also activated locally in obese adipose. Up-regulated expression of adhesion molecules on multiple cell types suggests that their increased interactions contribute to local activation of inflammatory processes within visceral obese adipose tissue. Interestingly, the heightened leukocyte-platelet-endothelial interactions were not observed in obese subcutaneous fat pads. Our results demonstrated the power of our imaging technique to analyze complex cellular interplays in vivo and to evaluate new therapeutic interventions against them. Results also indicate that visceral obese adipose tissue is an inflammatory site itself.

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