title: CL316,243 and cold stress induce heterogeneous expression of UCP1 mRNA and protein in rodent brown adipocytes.
abstract: Uncoupling protein 1 (UCP1), the mammalian thermogenic mitochondrial protein, is found only in brown adipocytes, but its expression by immunohistochemistry is not homogeneous. Here we present evidence that the non-homogeneous pattern of immunostaining for UCP1 (referred to as the "Harlequin phenomenon") is particularly evident after acute and chronic cold (4C) stimulus and after administration of a specific beta(3)-adrenoceptor agonist (CL316,243). Accordingly, mRNA in situ expression confirmed the UCP1 non-homogeneous pattern of gene activation under conditions of adrenergic stimulus. Furthermore, morphometric analysis of immunogold-stained thin sections showed that UCP1-gold particle density was different among neighboring brown adipocytes with mitochondria of the same size and density. When the adrenergic stimulus was reduced in warm-acclimated animals (28C), UCP1 protein and mRNA expression was reduced and consequently the Harlequin phenomenon was barely visible. These data suggest the existence of an alternative and controlled functional recruitment of brown adipocytes in acute adrenergically stressed animals, possibly to avoid heat and metabolic damage in thermogenically active cells. Of note, the heat shock protein heme oxygenase 1 (HO1) is heterogeneously expressed in adrenergically stimulated brown adipose tissue and, specifically, cells expressing strong immunoreactivity for UCP1 also strongly express HO1.
authors.affiliation: Institute of Normal Human Morphology, Faculty of Medicine, University of Ancona, Italy. cinti@popsci.unian.it
authors.forename: Saverio
authors.initials: S
authors.lastname: Cinti
authors.forename: Raffaella
authors.initials: R
authors.lastname: Cancello
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Zingaretti
authors.forename: Enzo
authors.initials: E
authors.lastname: Ceresi
authors.forename: Rita
authors.initials: R
authors.lastname: De Matteis
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
authors.forename: Jean
authors.initials: J
authors.lastname: Himms-Hagen
authors.forename: Daniel
authors.initials: D
authors.lastname: Ricquier
mesh_terms: D000064:Acclimatization; D017667:Adipocytes / Q000378:metabolism* / Q000648:ultrastructure; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003080:Cold Temperature; D004149:Dioxoles / Q000494:pharmacology*; D006361:Heating; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007473:Ion Channels; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D016253:Microscopy, Immunoelectron; D024101:Mitochondrial Proteins; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D022702:Receptors, Adrenergic, beta-3 / Q000187:drug effects; D013312:Stress, Physiological / Q000378:metabolism*; D000071256:Uncoupling Protein 1
chemical_list: D000318:Adrenergic beta-Agonists; D002352:Carrier Proteins; D004149:Dioxoles; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D022702:Receptors, Adrenergic, beta-3; C000604371:UCP1 protein, human; C000604373:Ucp1 protein, rat; D000071256:Uncoupling Protein 1; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1