Western style diet impairs entrance of blood-borne insulin-like growth factor-1 into the brain.

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.