title: Maternal Obesity in the Mouse Compromises the Blood-Brain Barrier in the Arcuate Nucleus of Offspring.
abstract: The arcuate nucleus (ARC) regulates body weight in response to blood-borne signals of energy balance. Blood-brain barrier (BBB) permeability in the ARC is determined by capillary endothelial cells (ECs) and tanycytes. Tight junctions between ECs limit paracellular entry of blood-borne molecules into the brain, whereas EC transporters and fenestrations regulate transcellular entry. Tanycytes appear to form a barrier that prevents free diffusion of blood-borne molecules. Here we tested the hypothesis that gestation in an obese mother alters BBB permeability in the ARC of offspring. A maternal high-fat diet model was used to generate offspring from normal-weight (control) and obese dams (OffOb). Evans Blue diffusion into the ARC was higher in OffOb compared with controls, indicating that ARC BBB permeability was altered. Vessels investing the ARC in OffOb had more fenestrations than controls, although the total number of vessels was not changed. A reduced number of tanycytic processes in the ARC of OffOb was also observed. The putative transporters, Lrp1 and dysferlin, were up-regulated and tight junction components were differentially expressed in OffOb compared with controls. These data suggest that maternal obesity during pregnancy can compromise BBB formation in the fetus, leading to altered BBB function in the ARC after birth.
authors.affiliation: Centre for Neuroendocrinology, Department of Anatomy, University of Otago School of Medical Sciences, Dunedin 9054, New Zealand.
authors.forename: Dong Won
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Centre for Neuroendocrinology, Department of Anatomy, University of Otago School of Medical Sciences, Dunedin 9054, New Zealand.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Glendining
authors.affiliation: Centre for Neuroendocrinology, Department of Anatomy, University of Otago School of Medical Sciences, Dunedin 9054, New Zealand.
authors.forename: David R
authors.initials: DR
authors.lastname: Grattan
authors.affiliation: Centre for Neuroendocrinology, Department of Anatomy, University of Otago School of Medical Sciences, Dunedin 9054, New Zealand.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Jasoni
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism* / Q000473:pathology*; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000473:pathology*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D059305:Diet, High-Fat; D005070:Evans Blue / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D007074:Immunoglobulin G / Q000378:metabolism; D007150:Immunohistochemistry; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000503:physiopathology*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D019108:Tight Junctions / Q000378:metabolism
chemical_list: D007074:Immunoglobulin G; D026901:Membrane Transport Proteins; D005070:Evans Blue