title: The metabolic organization of the adult human liver: a comparative study of normal, fibrotic, and cirrhotic liver tissue.
abstract: Little is known about the alterations of metabolic organization of the human liver tissue in chronic liver diseases. We therefore compared the distribution of the following zonal metabolic markers in 10 samples of normal liver tissue, 10 samples of fibrotic tissue, and 22 samples of cirrhotic tissue: (a) the enzymatic activities of glucose-6-phosphatase (G6P), lactate dehydrogenase (LDH), succinate dehydrogenase (SDH), nicotinamide-adenine-dinucleotide-phosphate [NAPH] dehydrogenase (ND), beta-hydroxybutyrate dehydrogenase (HBDH), and glutamate dehydrogenase (GDH); (b) the protein glutamine synthetase (GLS); and (c) albumin messenger RNA (mRNA). The normal human hepatic lobule was characterized by the periportal predominance of G6P and SDH enzymatic activities and albumin mRNAs, the perivenous predominance of ND and GDH, the restriction of GLS to a small perivenous compartment, and the predominanc of beta-HBDH at the contact of both portal tracts and centrilobular veins. In fibrosis, the overall metabolic organization of the normal liver tissue was retained. The expression of periportal markers predominated around enlarged portal tracts and that of perivenous markers around residual centrilobular veins. GLS was constantly detected at the contact of centrilobular veins. In cirrhotic nodules, no zonation was observed for most enzymatic activities or for albumin. Only G6P usually predominated at the periphery of the nodules. GLS was constantly undetectable. No difference accordingly to the etiology of the underlying disease was observed. In conclusion, the normal human hepatic lobule presents a marked metabolic zonation, preserved in fibrotic lesions, but lost in cirrhotic nodules. The alterations of the metabolic organization observed in cirrhosis might contribute to the pathogenesis of some of the metabolic disorders associated with advanced liver disease.
authors.affiliation: Laboratoire de Biologie Cellulaire and Unité INSERM, Faculté de Medecine Xavier Bichat, Université Denis Diderot, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Racine-Samson
authors.forename: J Y
authors.initials: JY
authors.lastname: Scoazec
authors.forename: A
authors.initials: A
authors.lastname: D'Errico
authors.forename: M
authors.initials: M
authors.lastname: Fiorentino
authors.forename: L
authors.initials: L
authors.lastname: Christa
authors.forename: A
authors.initials: A
authors.lastname: Moreau
authors.forename: C
authors.initials: C
authors.lastname: Roda
authors.forename: W F
authors.initials: WF
authors.lastname: Grigioni
authors.forename: G
authors.initials: G
authors.lastname: Feldman
mesh_terms: D000328:Adult; D015415:Biomarkers; D005260:Female; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D006391:Hemangioma / Q000201:enzymology / Q000473:pathology / Q000601:surgery; D006801:Humans; D006884:Hydroxybutyrate Dehydrogenase / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008103:Liver Cirrhosis / Q000201:enzymology* / Q000473:pathology; D008104:Liver Cirrhosis, Alcoholic / Q000201:enzymology / Q000473:pathology; D008113:Liver Neoplasms / Q000201:enzymology / Q000473:pathology / Q000556:secondary / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009252:NADPH Dehydrogenase / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D012016:Reference Values; D012709:Serum Albumin / Q000096:biosynthesis; D013385:Succinate Dehydrogenase / Q000378:metabolism
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D012709:Serum Albumin; D007770:L-Lactate Dehydrogenase; D006884:Hydroxybutyrate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase; D013385:Succinate Dehydrogenase; D005969:Glutamate Dehydrogenase; D009252:NADPH Dehydrogenase; D005974:Glutamate-Ammonia Ligase