Persistence of blood-to-brain transport of leptin in obese leptin-deficient and leptin receptor-deficient mice

In lean CD-1 mice, leptin is delivered into the brain by a saturable transp ort mechanism. Previous work has shown that obesity is associated with decr eased leptin transport. Here, we investigated the transport of leptin acros s the blood-brain barrier (BBB) in two murine models of obesity. Radioiodin ated leptin was intravenously injected into ob/ob (no leptin production) an d db/db thigh leptin levels, but no long-form leptin receptor) mutant mice and their lean controls. In all groups, the labeled polypeptide was transpo rted across the BBB by a saturable mechanism. The rates of transport were n ot significantly different between the mutant strains and their lean contro ls. The results demonstrate that leptin transport persists in the absence o f production of the endogenous polypeptide or its signal-transducing recept or and suggest that the impaired transport previously seen is not directly explained by only obesity or alterations in serum plasma levels. (C) 2000 E lsevier Science B.V. All rights reserved.