In Vivo Imaging Reveals Adipose Tissue Inflammation in Obesity and Multi-cellular Processes of Developing Thrombus

Abstract

  The metabolic syndrome is a major risk factor of cardiovascular events, and obese visceral adipose tissue remodeling based on chronic inflammation plays a central role. To assess dynamic interplay between multiple cell types in obese adipose tissue, a visualization technique in vivo was developed. By this technique we identified inflammatory cell clusters associated with angiogenesis and adipogenesis in obese adipose tissue. We also found increased leukocyte-platelet-endothelial cell interactions in obese adipose tissue microcirculation, which were indicative of local chronic inflammation. Moreover, we found that large numbers of CD8⁺ effector T cells infiltrated into obese adipose tissue. Immunological and genetic depletion of CD8⁺ T cells reduced inflammatory (M1) macrophage infiltration and adipose tissue inflammation, and ameliorated systemic insulin resistance. Infiltration of CD8⁺ T cells is essential for inflammatory macrophage recruitment into obese adipose tissue, and the initiation and development of inflammation therein. Our results clearly demonstrate the power of our imaging technique to analyze complex cellular interplay in vivo, especially parenchymal and stromal cell crosstalk, and to evaluate new therapeutic interventions against conditions arising from these interactions.