Since the late 1950s, transport of bile in the liver has been described by the "osmotic concept," according to which bile flows into the canaliculi toward the ducts, countercurrent to the blood flow in the sinusoids. However, because of the small size of canaliculi, it was so far impossible to observe, let alone to quantify this process. Still, "osmotic canalicular flow" was a sufficient and plausible explanation for the clearance characteristics of a wide variety of choleretic compounds excreted in bile. Imaging techniques have now been established that allow direct flux analysis in bile canaliculi of the intact liver in living organisms. In contrast to the prevailing osmotic concept these analyses strongly suggest that the transport of small molecules in canalicular bile is diffusion dominated, while canalicular flow is negligibly small. In contrast, with the same experimental approach, it could be shown that in the interlobular ducts, diffusion is augmented by flow. Thus, bile canaliculi can be compared to a standing water zone that is connected to a river. The seemingly subtle difference between diffusion and flow is of relevance for therapy of a wide range of liver diseases including cholestasis and NAFLD. Here, we incorporated the latest findings on canalicular solute transport, and align them with extant knowledge to present an integrated and explanatory framework of bile flux that will undoubtedly be refined further in the future.
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http://dx.doi.org/10.1002/hep.32027 | DOI Listing |
Toxicol Rep
December 2024
Department of Pathology, College of Medicine, University of Baghdad, Baghdad, Iraq.
Development
November 2024
Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
During liver development, bipotential progenitor cells called hepatoblasts differentiate into hepatocytes or cholangiocytes. Hepatocyte differentiation is uniquely associated with multi-axial polarity, enabling the anisotropic expansion of apical lumina between adjacent cells and formation of a three-dimensional network of bile canaliculi. Cholangiocytes, the cells forming the bile ducts, exhibit the vectorial polarity characteristic of epithelial cells.
View Article and Find Full Text PDFBiofabrication
October 2024
Mimetas US, INC, Gaithersburg, MD 20878, United States of America.
Drug discovery for complex liver diseases faces alarming attrition rates. The lack of non-clinical models that recapitulate key aspects of liver (patho)-physiology is likely contributing to the inefficiency of developing effective treatments. Of particular notice is the common omission of an organized microvascular component despite its importance in maintaining liver function and its involvement in the development of several pathologies.
View Article and Find Full Text PDFComp Biochem Physiol Part D Genomics Proteomics
December 2024
College of Life Science, Shaanxi Normal University, Xi'an 710119, China. Electronic address:
Bile acids are crucial for lipid metabolism and their composition and metabolism differ among species. However, there have been no data on the differences in the composition and metabolism of bile acids between aquatic larvae and terrestrial adults of amphibians. This study explored the differences in composition and metabolism of bile acid between Bufo gargarizans larvae and adults.
View Article and Find Full Text PDFStem Cell Res Ther
August 2024
Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8102, Japan.
Background: Liver disease imposes a significant medical burden that persists due to a shortage of liver donors and an incomplete understanding of liver disease progression. Hepatobiliary organoids (HBOs) could provide an in vitro mini-organ model to increase the understanding of the liver and may benefit the development of regenerative medicine.
Methods: In this study, we aimed to establish HBOs with bile duct (BD) structures and mature hepatocytes (MHs) using human chemically induced liver progenitor cells (hCLiPs).
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