title: Apolipoprotein E knockout mice have accentuated malnutrition with mucosal disruption and blunted insulin-like growth factor I responses to refeeding.
abstract: Apolipoprotein E (apoE) is synthesized mainly in the liver and in the brain and is critical for cholesterol metabolism and recovery from brain injury. However, although apoE mRNA increases at birth, during suckling, and after fasting in rat liver, little is known about its role in early postnatal development. Using an established postnatal malnutrition model and apoE knock-out (ko) mice, we examined the role of apoE in intestinal adaptation responses to early postnatal malnutrition. Wild-type and apoE-ko mice were separated from their lactating dams for defined periods each day (4 hours on day 1, 8 hours on day 2, and 12 hours thereafter). We found significant growth deficits, as measured by weight gain or tail length, in the apoE-ko mice submitted to a malnutrition challenge, as compared with malnourished wild type, especially during the second week of postnatal development (P< .05). In addition, apoE-ko animals failed to show growth catch-up after refeeding, compared with wild-type malnourished controls. Furthermore, we found shorter crypts and reduced villus height and area in the apoE-ko malnourished mice, compared with controls, after refeeding. Insulinlike growth factor 1 expression was also blunted in the ileum in apoE-ko mice after refeeding, compared with wild-type controls, which exhibited full insulinlike growth factor 1 expression along the intestinal crypts, villi, and in the muscular layer. Taken together, these findings suggest the importance of apoE in coping with a malnutrition challenge and during the intestinal adaptation after refeeding.
authors.affiliation: Center for Global Health, Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA 22908-1379, USA ; Department of Morphology, Federal University of Ceará, Fortaleza, CE 60430-270, Brazil ; Institute of Biomedicine and Clinical Research Unit-University Hospital, Federal University of Ceará, Fortaleza, CE 60430-270, Brazil.
authors.forename: Reinaldo B
authors.initials: RB
authors.lastname: Oriá
authors.affiliation: Center for Global Health, Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA 22908-1379, USA.
authors.forename: Carlos Meton G
authors.initials: CM
authors.lastname: Vieira
authors.affiliation: Center for Global Health, Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA 22908-1379, USA.
authors.forename: Relana C
authors.initials: RC
authors.lastname: Pinkerton
authors.affiliation: Physiology and Pharmacology Department, Federal University of Ceará, Fortaleza, CE 60430-270, Brazil.
authors.forename: Carlos M
authors.initials: CM
authors.lastname: de Castro Costa
authors.affiliation: Pathology Department, University of Virginia, Charlottesville, VA 22908-1379, USA.
authors.forename: Maria Beatriz
authors.initials: MB
authors.lastname: Lopes
authors.affiliation: Pathology Department, University of Virginia, Charlottesville, VA 22908-1379, USA.
authors.forename: Isa
authors.initials: I
authors.lastname: Hussaini
authors.affiliation: Radiology Department, University of Virginia, Charlottesville, VA 22908-1379, USA.
authors.forename: Weibin
authors.initials: W
authors.lastname: Shi
authors.affiliation: Department of Morphology, Federal University of Ceará, Fortaleza, CE 60430-270, Brazil.
authors.forename: Gerly A C
authors.initials: GA
authors.lastname: Brito
authors.affiliation: Center for Global Health, Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA 22908-1379, USA ; Institute of Biomedicine and Clinical Research Unit-University Hospital, Federal University of Ceará, Fortaleza, CE 60430-270, Brazil.
authors.forename: Aldo A M
authors.initials: AA
authors.lastname: Lima
authors.affiliation: Center for Global Health, Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA 22908-1379, USA ; Department of Morphology, Federal University of Ceará, Fortaleza, CE 60430-270, Brazil.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Guerrant
keywords: ApoE; Growing mice; IGF-1; Malnutrition; Small intestine