Abstract
Hepatobiliary metabolism is one of the major functions of the liver. However, little is known of the relationship between the physiological location of the hepatocytes and their metabolic potential. By the combination of time-lapse multiphoton microscopy and first order kinetic constant image analysis, the hepatocellular metabolic rate of the model compound 6-carboxyfluorescein diacetate (6-CFDA) is quantified at the single cell level. We found that the mouse liver can be divided into three zones, each with distinct metabolic rate constants. The sinusoidal uptake coefficients k1 of Zones 1, 2, and 3 are respectively 0.239 ± 0.077, 0.295 ± 0.087, and 0.338 ± 0.133 min-1, the apical excreting coefficients k2 of Zones 1, 2, and 3 are 0.0117 ± 0.0052, 0.0175 ± 0.0052, and 0.0332 ± 0.0195 min-1, respectively. Our results show not only the existence of heterogeneities in hepatobiliary metabolism, but they also show that Zone 3 is the main area of metabolism.
Highlights
The liver, positioned between the intestine which absorbs nutrients and other organs which utilize nutrients, holds an extraordinary position in the metabolism of ingested nutrients
After injecting anesthetized mice with rhodamine B isothiocyanate (RITC)-dextran through jugular vein, we tracked the motion of nonfluorescent erythrocytes using time-lapse video microscopy and visualized direction of blood flow from portal tracts to central veins (Fig. 8, Appendix 3), thereby identifying the locations of the portal and central veins (Fig. 1) for defining hepatic acinus and its relative position to hexagonal lobules
To quantify the metabolic rate of 6-carboxyfluorescein diacetate (6-CFDA) in hepatocytes, a first-order, kinetic model was used to describe the kinetics of 6-CF fluorescence within the hepatocytes
Summary
The liver, positioned between the intestine which absorbs nutrients and other organs which utilize nutrients, holds an extraordinary position in the metabolism of ingested nutrients. Blood is supplied via the portal vein (about 80% of flow) and the hepatic artery (about 20% of flow), the liver drains its metabolites into the bile system or inferior vena cava. The hepatocytes form a trabecular network, facing the sinusoids with their basolateral surface and forming the bile canaliculi with their apical membranes. Metabolites, such as fatty acid or drugs, are metabolized and excreted by hepatocytes into the bile system. Clarification of the metabolic and functional potential among cells within different compartments of the liver is of significant interest in hepatology [1,2,3]
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