In vivo imaging reveals inflammatory and immune processes of adipose tissue obesity.

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Metabolic syndrome is a major risk factor of cardiovascular events, and obese visceral adipose tissue remodeling and malfunctioning based on chronic inflammation and local immunological changes plays a central role. To assess dynamic interplay between multiple cell-types in obese adipose, a visualization technique in vivo was therefore developed. In vivo imaging revealed close spatial and temporal interrelationships between angiogenesis and adipogenesis in obese adipose, and these inflammatory cell clusters included inflammatory "M1" macrophages). Increased leukocyte-platelet-endothelial cell interactions in the microcirculation of obese adipose were also observed, a hallmark of inflammation. The activation of platelet and increased adhesion molecule contribute to the inflammatory cellular dynamics, such as "rolling and adhesion" of leukocyte and platelet. We also found that large numbers of CD8+ effector T cells infiltrated into obese adipose. The infiltration by CD8+ T cells preceded the accumulation of macrophages, and immunological and genetic depletion of CD8+ T cells reduced macrophage infiltration and adipose tissue inflammation, and ameliorated systemic insulin resistance. CD8+ T cells contribute to the macrophage recruitment in obese adipose tissue, and adipose tissues inflammation in obesity. This imaging technique can be applied to many diseases including thrombosis. Our results clearly demonstrated the power of our imaging technique to analyze complex cellular interplays in vivo and to evaluate new therapeutic interventions against them.