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.