title: Inbuilt mechanisms for overcoming functional problems inherent in hepatic microlobular structure.
abstract: The spherical anatomy of human and rat liver lobules implies that more central cells have less time to carry out their function than more peripherally located cells because blood flows past them more rapidly. This problem could be overcome if more centrilobular cells could operate at higher temperatures than periportal cells. This study presents evidence for such a temperature gradient. Firstly, we use mathematical modelling to demonstrate that temperature increases towards the centre of the lobule. Secondly, we examine the distribution of a heat-generating protein and of a heat-sensitive protein across the rat and human liver lobules. Double-antibody staining of healthy liver from rat and human was used for visual scoring and for automated histomorphometric quantitation of the localisation of uncoupling protein-2 (known to generate heat) and of the transient receptor potential-v4 protein (known as a highly temperature-sensitive membrane protein). Both these proteins were found to be located predominantly in the centrilobular region of liver lobules. These findings support the suggestion that temperature gradients across the liver lobule may have evolved as a solution to the problem of reduced contact time between blood and cells at the centre as compared to the periphery of mammalian liver lobules.
authors.affiliation: Centre for Diabetes, Bart's and The London School of Medicine and Dentistry, Blizard Institute for Cell and Molecular Sciences, Queen Mary University of London, Newark Street, London E1 2AT, UK.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Cohen
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Brown
authors.forename: Carole
authors.initials: C
authors.lastname: Nickols
authors.forename: Pauline
authors.initials: P
authors.lastname: Levey
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Boucher
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Greenwald
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
mesh_terms: D000328:Adult; D000818:Animals; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007473:Ion Channels / Q000378:metabolism*; D008099:Liver / Q000033:anatomy & histology* / Q000098:blood supply / Q000378:metabolism / Q000502:physiology*; D008102:Liver Circulation / Q000502:physiology; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000378:metabolism*; D008954:Models, Biological; D051381:Rats; D017208:Rats, Wistar; D050916:TRPV Cation Channels / Q000378:metabolism*; D013696:Temperature; D000071246:Uncoupling Protein 2; D055815:Young Adult
chemical_list: D007473:Ion Channels; D024101:Mitochondrial Proteins; D050916:TRPV Cation Channels; C416986:TRPV4 protein, human; C000604389:UCP2 protein, human; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2