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In vivo multi-cellular and molecular imaging revealed obese adipose tissue
remodeling and inflammatory cellular dynamics in metabolic syndrome
Satoshi Nishimura
Department of Cardiovascular Medicine, The University of Tokyo
PRESTO, Japan Science and Technology Agency
Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan
KEY WORDS: in vivo imaging, remodeling, inflammation, angiogenesis, laser
confocal
To elucidate the molecular mechanisms of pathological conditions consisted
by the complicated and multi-cellular abnormal interactions in remodeling
tissues, an intravital visualization technique, based on laser confocal
microscopy was therefore needed and developed. It enabled us to precisely
evaluate the three-dimensional structures in living tissue, and the
multi-cellular dynamics in vivo with high time and spatial resolutions. Using
this technique, we focus on the metabolic syndrome and how obese adipose
tissue plays a bad role in obesity. Adipose tissue contains multiple cell
types including adipocytes, macrophages, lymphocytes, endothelium, and blood
cells, and all of them are specifically visualized in vivo. Our novel
technique clearly visualized single platelets in vivo for the first time!
Their multi-cellular interactions are important in normal adipose tissue
function, and malfunctioning in obesity. First, we elucidated the close
spatial and temporal relationships between angiogenesis and adipogenesis, and
both were augmented in obesity, (we referred this as "obese adipose
tissue remodeling", Fig. B). In microcirculation of obese adipose, close
interactions of activated platelets, leukocytes, and endothelial cells in the
vessel walls were also observed in obesity, which were indicative of
activation of the leukocyte adhesion cascade, a hallmark of inflammation (Fig.
C). Local platelet activation and upregulated expression of adhesion molecules
contribute to these inflammatory processes in obese adipose. Recently, we also
clarified that the CD8+ T cells and macrophage interactions were important for
this inflammatory processes. Using our new imaging technique to analyze the
complex cellular interplay in vivo, we clearly showed that adipose tissue
obesity is an inflammatory disease and it also enabled us to evaluate
potential therapeutic interventions against it.
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