UP-REGULATION OF BLOOD-BRAIN-BARRIER SHORT-FORM LEPTIN RECEPTOR GENE-PRODUCTS IN RATS FED A HIGH-FAT DIET

Leptin is a 16-kDa protein synthesized in adipose tissue that produces a satiety effect in the CNS. Leptin may gain access to the brain via receptor-mediated transport through the blood-brain barrier (BBB), and the BBB leptin receptor (OBR) may regulate the availability of circul ating leptin to brain cells. The aim of the present study was twofold: first, to identify the OBR isoform expressed at the BBB, i.e., short, or ''a,'' and long, or ''b,'' form; and second, to compare the abunda nce of the BBB OBR mRNA and protein between control and high fat-fed r ats. RT-PCR with isoform-specific primers showed that OBRa is the most abundant isoform at the BBB. BBB OBRa transcript content was markedly increased in high fat-fed rats compared with controls (11-fold), and no changes were observed in the expression of the internal standard co ntrol actin. The high fat feeding induction of OBR mRNA was correlated with an increase in the immunoreactive BBB OBR determined by immunocy tochemistry using an all-isoform reactive antibody in high fat-fed obe se rats. This investigation demonstrates (a) the OBRa is the principal leptin receptor expressed at the BBB and (b) this BBB OBR isoform is up-regulated by a high fat diet.