Tokyo, Japan. Obese individuals are at increased risk of developing a combination of medical disorders associated with type 2 diabetes and a heart disease known as the metabolic syndrome. Recent studies suggest that fat (adipose) tissue obesity induces an inflammatory state that is crucial to the development of the metabolic syndrome. Satoshi Nishimura, Ichiro Manabe, and colleagues at the University of Tokyo, Japan developed a new technique for examining mouse adipose tissue.

 

The study team used instrumentation based on confocal laser microscopy to visualize cellular interactions within mouse adipose tissue in vivo (in the the living organism) with high resolution. This same approach has the potential to visualize fat cell interactions in a variety of human organs and appendages.

 

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In vivo imaging in mice reveals local cell dynamics and inflammation in obese adipose tissue. Satoshi Nishimura, Ichiro Manabe, Mika Nagasaki, Kinya Seo, Hiroshi Yamashita, Yumiko Hosoya, Mitsuru Ohsugi, Kazuyuki Tobe, Takashi Kadowaki, Ryozo Nagai, Seiryo Sugiura. J. Clin. Invest. doi: 10.1172 / JCI33328. [Abstract/PDF below]

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A beam of laser light is focused into a small point at the focal plane of the specimen, for example inside a cell loaded with a probe. A computer controlled scanning mirror can move or scan this beam in the X-Y direction at the focal plane. Thus the name scanning microscopy.

 

The florescent emission created by the point as it scans in the focal plane is detected  by a photon multiplier tube. This detection input is reconstructed by computer hardware into an image.  

 

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Adipose tissue microcirculation visualized by in vivo molecular imaging. The erythrocyte, leukocyte and platelet cell dynamics can be visualized with high time and spatial resolutions in adipose tissue by in vivo molecular imaging method. Left: Capillary microcirculation visualized by FITC-dextran (green), and anti-CD41 (red). Right: Post capillary visualized by FITC-dextran.

 

Scale bars represent 10 µm (10 micrometres). One micrometre equals one millionth of a metre, a unit commonly known as a micron. The scientific notation is 1×10−6 m, meaning 1 / 1,000,000 m.

 

Photo: Courtesy of Satoshi Nishimura, Department of Cardiovascular Medicine, the University of Tokyo.

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Changes that indicated inflammation were observed in the adipose, or fat, tissue of both mice that were obese through genetic mutations and mice that were obese as a result of being fed a high-fat diet.

 

In addition, the investigators noted something interesting in the thin layer of cells that line the interior surface of blood vessels. This is the endothelium, an interface between circulating blood in the cavity (lumen) and the rest of the vessel wall. The endothelial cells of the adipose tissue could be seen interacting with inflammatory cells known as macrophages, the cells that clean up debris and other remains.

 

This observation indicates a central role for interplay between these two cell types in the activation of inflammation within the adipose tissue. This indicates that adipose tissue obesity is an inflammatory disease. The authors suggest that this technique might allow the use of mice to test potential therapeutics for the treating diseases stemming from adipose tissue obesity.

 

The investigative team published their findings in the Journal of Clinical Investigation.

 

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In vivo imaging in mice reveals local cell dynamics and inflammation in obese adipose tissue. Satoshi Nishimura, Ichiro Manabe, Mika Nagasaki, Kinya Seo, Hiroshi Yamashita, Yumiko Hosoya, Mitsuru Ohsugi, Kazuyuki Tobe, Takashi Kadowaki, Ryozo Nagai, Seiryo Sugiura. J. Clin. Invest. doi: 10.1172 / JCI33328.

 

Abstract. To assess physiological and pathophysiological events that involve dynamic interplay between multiple cell types, real-time, in vivo analysis is necessary. We developed a technique based on confocal laser microscopy that enabled us to analyze and compare the 3-dimensional structures, cellular dynamics, and vascular function within mouse lean and obese adipose tissue in vivo with high spatiotemporal resolution. We found increased leukocyte-EC-platelet interaction in the microcirculation of obese visceral adipose tissue in ob/ob and high-fat diet–induced obese mice. These changes were indicative of activation of the leukocyte adhesion cascade, a hallmark of inflammation. Local platelet activation in obese adipose tissue was indicated by increased P-selectin expression and formation of monocyte-platelet conjugates. We observed upregulated expression of adhesion molecules on macrophages and ECs in obese visceral adipose tissue, suggesting that interactions between these cells contribute to local activation of inflammatory processes. Furthermore, administration of anti–ICAM-1 antibody normalized the cell dynamics seen in obese visceral fat. This imaging technique to analyze the complex cellular interplay within obese adipose tissue allowed us to show that visceral adipose tissue obesity is an inflammatory disease. In addition, this technique may prove to be a valuable tool to evaluate potential therapeutic interventions.

 

[ Full Text (PDF) ]

 

 

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