title: In vivo vitamin C deficiency in guinea pigs increases ascorbate transporters in liver but not kidney and brain.
abstract: Moderate vitamin C (vitC) deficiency (plasma concentrations less than 23 μmol/L) affects as much as 10% of adults in the Western World and has been associated with an increased mortality in disease complexes such as cardiovascular disease and the metabolic syndrome. The distribution of vitC within the body is subjected to complex and nonlinear pharmacokinetics and largely depends on the sodium-dependent vitC-specific transporters, sodium-dependent vitamin C transporter 1 (SVCT1) and sodium-dependent vitamin C transporter 2 (SVCT2). Although currently not established, it is likely to expect that a state of deficiency may affect the expression of these transporters to preserve vitC concentrations in specific target tissues. We hypothesized that diet-induced states of vitC deficiency lead to alterations in the messenger RNA (mRNA) and/or protein expression of vitC transporters, thereby regulating vitC tissue distribution. Using guinea pigs as a validated model, this study investigated the effects of a diet-induced vitC deficiency (100 mg vitC/kg feed) or depletion (0 mg vitC/kg feed) on the expression of transporters SVCT1 and SVCT2 in selected tissues and the transport from plasma to cerebrospinal fluid (CSF). In deficient animals, SVCT1 was increased in the liver, whereas a decreased SVCT1 expression but increased SVCT2 mRNA in livers of depleted animals suggests a shift in transporter expression as response to the diet. In CSF, a constant plasma:CSF ratio shows unaltered vitC transport irrespective of dietary regime. The study adds novel information to the complex regulation maintaining vitC homeostasis in vivo during states of deficiency.
authors.affiliation: Section of Experimental Animal Models, Department of Veterinary Disease Biology, Faculty of Health & Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ditte
authors.initials: D
authors.lastname: Søgaard
authors.affiliation: Section of Experimental Animal Models, Department of Veterinary Disease Biology, Faculty of Health & Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Maiken M
authors.initials: MM
authors.lastname: Lindblad
authors.affiliation: Section of Experimental Animal Models, Department of Veterinary Disease Biology, Faculty of Health & Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Maya D
authors.initials: MD
authors.lastname: Paidi
authors.affiliation: Section of Experimental Animal Models, Department of Veterinary Disease Biology, Faculty of Health & Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Stine
authors.initials: S
authors.lastname: Hasselholt
authors.affiliation: Section of Experimental Animal Models, Department of Veterinary Disease Biology, Faculty of Health & Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Lykkesfeldt
authors.affiliation: Section of Experimental Animal Models, Department of Veterinary Disease Biology, Faculty of Health & Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: ptn@sund.ku.dk.
authors.forename: Pernille
authors.initials: P
authors.lastname: Tveden-Nyborg
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism / Q000493:pharmacokinetics*; D001206:Ascorbic Acid Deficiency / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D004032:Diet; D005260:Female; D006168:Guinea Pigs; D006706:Homeostasis; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D060347:Sodium-Coupled Vitamin C Transporters / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution; D014815:Vitamins / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism / Q000493:pharmacokinetics*
chemical_list: D012333:RNA, Messenger; D060347:Sodium-Coupled Vitamin C Transporters; D014815:Vitamins; D001205:Ascorbic Acid
keywords: Ascorbic acid [D02.241.511.902.107]; Brain [A08.186.211]; Deficiency diseases [C18.654.521.500]; Guinea pig; Malnutrition [C18.654.521]