Hepatocytes located in the periportal and perivenous zones of the liver lobule show remarkable differences in the levels and activities of various enzymes and other proteins. To analyze global gene expression patterns of periportal and perivenous hepatocytes, enriched populations of the two cell types were isolated by combined collagenase/digitonin perfusion from mouse liver and used for microarray analysis. In total, 198 genes and expressed sequences were identified that demonstrated a >/= 2-fold difference in expression between hepatocytes from the two different zones of the liver. A subset of 20 genes was additionally analyzed by real-time RT-PCR, validating the results obtained by the microarray analysis. Several of the differentially expressed genes encoded key enzymes of intermediary metabolism, including those involved in glycolysis and gluconeogenesis, fatty acid degradation, cholesterol and bile acid metabolism, amino acid degradation and ammonia utilization. In addition, several enzymes of phase I and phase II of xenobiotic metabolism were differentially expressed in periportal and perivenous hepatocytes. Our results confirm previous findings on metabolic zonation in liver, and extend our knowledge of the regulatory mechanisms at the transcriptional level.
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http://dx.doi.org/10.1111/j.1742-4658.2006.05503.x | DOI Listing |
Metabolism
May 2024
Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, United States of America. Electronic address:
Liver zonation characterizes the separation of metabolic pathways along the lobules and is required for optimal hepatic function. Wnt signaling is a master regulator of spatial liver zonation. A perivenous-periportal Wnt activity gradient orchestrates metabolic zonation by activating gene expression in perivenous hepatocytes, while suppressing gene expression in their periportal counterparts.
View Article and Find Full Text PDFActa Biomater
November 2023
Department of Health Technology, DTU Health Tech, Technical University of Denmark, Kgs, Lyngby, Denmark. Electronic address:
Hepatic in vitro models that accurately replicate phenotypes and functionality of the human liver are needed for applications in toxicology, pharmacology and biomedicine. Notably, it has become clear that liver function can only be sustained in 3D culture systems at physiologically relevant cell densities. Additionally, drug metabolism and drug-induced cellular toxicity often follow distinct spatial micropatterns of the metabolic zones in the liver acinus, calling for models that capture this zonation.
View Article and Find Full Text PDFBraz J Med Biol Res
September 2023
Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Maringá, PR, Brasil.
The impact of linseed oil as a lipid source on liver disease induced by a high-carbohydrate diet (HCD) was evaluated. Adult male Swiss mice received an HCD containing carbohydrates (72.1%), proteins (14.
View Article and Find Full Text PDFJ Lipid Res
August 2023
Department of Cell Death and Proliferation, Institute of Biomedical Research of Barcelona (IIBB), CSIC, Barcelona, Spain; Liver Unit, Hospital Clinic I Provincial de Barcelona, Barcelona, Spain; Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Barcelona, Spain; CIBEREHD, Madrid, Spain; Department of Medicine, Keck School of Division of Gastrointestinal and Liver Disease, University of Southern California, Los Angeles, CA, USA. Electronic address:
Curr Protoc
February 2023
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Oxygen is an essential regulator of cellular function and phenotype. Despite its importance, the incorporation of physiologically relevant oxygen tensions is often overlooked in experimental setups. Ambient oxygen tensions (pO ∼152 mmHg) are significantly higher than those in the alveolar-capillary barrier of the lung, which is the most oxygen-rich interface in the body (pO ∼104 mmHg).
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