title: Megalin mediates the transport of leptin across the blood-CSF barrier.
abstract: Leptin, a peptide hormone secreted by adipose tissue, exhibits a large range of central and peripheral actions. It has been proposed that the participation of leptin in diseases such as obesity is due to, at least in part, its impaired transport across the blood-brain barrier (BBB). Since, the mechanisms by which brain takes up leptin remain unclear, we set out to study how leptin may cross the BBB. We have used different immunoassays and lentiviral vectors to analyze the role of megalin in the transport of leptin in rodents and humans. We demonstrate that circulating leptin is transported into the brain by binding to megalin at the choroid plexus epithelium. Indeed, the downregulation of megalin expression in physiological and pathological situations such as aging and Alzheimer's disease was correlated with poor entry of leptin into the brain. Moreover, amyloid beta (Abeta) deposits of choroid plexus could be disturbing megalin function. The present data indicate that leptin represents a novel megalin ligand of importance in the levels and therapeutic actions of leptin into the brain.
authors.affiliation: Department of Biochemistry, ICBS, University Federal do Rio Grande de Sul, Porto Alegre, RS, Brazil. dietrich.mo@gmail.com
authors.forename: Marcelo O
authors.initials: MO
authors.lastname: Dietrich
authors.forename: Carlos
authors.initials: C
authors.lastname: Spuch
authors.forename: Dessire
authors.initials: D
authors.lastname: Antequera
authors.forename: Izaskun
authors.initials: I
authors.lastname: Rodal
authors.forename: Justo G
authors.initials: JG
authors.lastname: de Yébenes
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Molina
authors.forename: Felix
authors.initials: F
authors.lastname: Bermejo
authors.forename: Eva
authors.initials: E
authors.lastname: Carro
mesh_terms: D000368:Aged; D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002555:Cerebrospinal Fluid / Q000378:metabolism*; D002831:Choroid Plexus / Q000378:metabolism*; D005260:Female; D006801:Humans; D020738:Leptin / Q000378:metabolism*; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction
chemical_list: D020738:Leptin; D026561:Low Density Lipoprotein Receptor-Related Protein-2