title: Western style diet impairs entrance of blood-borne insulin-like growth factor-1 into the brain.
abstract: It is increasingly recognized that life-style factors, such as physical exercise or diet influence brain health. In the present work we analyzed the effect of a western-style diet ("cafeteria diet") on the entrance to the brain of circulating IGF-1, a neuroprotective agent that has been related to different neurodegenerative diseases. Rats under a cafeteria diet showed reduced passage of systemic IGF-1 across the choroid plexus, a main site of IGF-1 entrance into the brain through the cerebrospinal fluid. Furthermore, the IGF-1 receptor at the choroid plexus of rats fed with a cafeteria diet showed enhanced sensitivity toward IGF-1 while receptor levels remained unchanged. Examination of possible mechanisms underlying reduced entrance of systemic IGF-1 to the brain showed that triglycerides that increased in blood after a cafeteria diet, diminished the passage of IGF-1 across choroid plexus epithelia. This effect of triglycerides was achieved by altering the interaction of IGF-1 with megalin, a choroid plexus transporter involved in transcytosis of IGF-1 from the circulation into the brain. Reduced brain entrance of circulating IGF-1 elicited by a western-style diet suggests that the higher incidence of brain diseases related to inadequate diets is due in part to diminished neurotrophic support.
authors.affiliation: Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Marcelo O
authors.initials: MO
authors.lastname: Dietrich
authors.forename: Alexandre
authors.initials: A
authors.lastname: Muller
authors.forename: Marta
authors.initials: M
authors.lastname: Bolos
authors.forename: Eva
authors.initials: E
authors.lastname: Carro
authors.forename: Marcos L
authors.initials: ML
authors.lastname: Perry
authors.forename: Luis V
authors.initials: LV
authors.lastname: Portela
authors.forename: Diogo O
authors.initials: DO
authors.lastname: Souza
authors.forename: Ignacio
authors.initials: I
authors.lastname: Torres-Aleman
mesh_terms: D000821:Animal Feed; D000818:Animals; D001812:Blood-Brain Barrier; D001835:Body Weight; D004032:Diet / Q000208:ethnology*; D007334:Insulin-Like Growth Factor I / Q000493:pharmacokinetics*; D008055:Lipids / Q000097:blood; D008297:Male; D023421:Models, Animal; D051381:Rats; D012147:Restaurants
chemical_list: D008055:Lipids; D007334:Insulin-Like Growth Factor I