Abstract
Brown adipose tissue (BAT), which is composed of thermogenic brown adipocytes (BA) and non-parenchymal components including vasculatures and extracellular matrix, contribute to the maintenance of body temperature. BAT distribution is detected by positron emission tomography-computed tomography (PET/CT) using 18F-fluorodeoxy glucose (18F-FDG) or single-photon-emission computed tomography-computed tomography (SPECT/CT) using [123/125I]-beta-methyl-p-iodophenyl-pentadecanoic acid. Although sympathetic nerve activity and thermogenic capacity of BA is downregulated under fasting conditions in mice, fasting-dependent structural changes and fluid kinetics of BAT remain unknown. Here we show that the fasting induces fine and reversible structural changes in the non-parenchymal region in murine BAT with widened intercellular spaces and deformed collagen bands as revealed by electron microscopy. Interestingly, a newly introduced near infrared fluorescent probe of single-walled carbon nanotubes (CNTs) coated with phospholipid polyethylene glycol (PLPEG) easily demonstrated enhanced vascular permeability in BAT by the fasting. PLPEG-CNTs extravasated and remained in intercellular spaces or further redistributed in parenchymal cells in fasted mice, which is a previously unknown phenomenon. Thus, PLPEG-CNTs provide a powerful tool to trace fluid kinetics in sub-tissue levels.
Highlights
Changes might possibly take place to enhance glucose accumulations in Brown adipose tissue (BAT) independently of the level of sympathetic nerve activity
Fasting-induced accumulation of phospholipid polyethylene glycol (PLPEG)-carbon nanotubes (CNTs) in BATs coupled with specific morphological changes
Bright CNT-fluorescent spots were detected in the pericapillary space (Fig. 6Bd, red arrow heads) in addition to the capillary lumen (Fig. 6Bd, red asterisk). These results indicate that the extravasation of PLEG-CNTs was induced by the fasting in interscapular BAT (iBAT), and PLPEG-CNTs diffused into the intercellular spaces and subsequently entered the brown adipocytes (BA)
Summary
Changes might possibly take place to enhance glucose accumulations in BAT independently of the level of sympathetic nerve activity. A new probe of single-walled carbon nanotubes (CNTs)[6,7] is known to emit fluorescence in the near infrared (NIR) region around 1000–1400 nm[8], and works as an excellent probe when coated with phospholipid polyethylene glycol (PLPEG-CNT) for vascular imaging by following reasons Light in this region can penetrate deeply into the body due to its low absorption and is weakly scattered by biomolecules. Intravenously administrated PLPEG-CNT fluorescent probe revealed that the vasculature permeability in BAT was enhanced by the fasting This unexpected finding presents a potential of PLPEG-CNT as a new tool to examine fluid kinetics in sub-tissue levels
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