OBJECTIVE:

Leptin inhibits appetite and reduces body weight. However, subcutaneous leptin administration is not very effective on weight reduction. The present studies were undertaken to test the hypotheses that nasally administered leptin effectively accesses to the brain and inhibits appetite.

METHODS:

Recombinant leptin (0.5 mg/rat) was administered into the bilateral nasal spaces of rats (in). Changes in serum immunoreactive leptin (IRL) and cerebrospinal fluid (CSF)-IRL concentrations after in leptin administration were compared after intraperitoneal (ip) administration. The influence of 0.1 or 0.5% lysophosphatidylcholine (LPC) as an optimizer of leptin absorption was examined. The anorexic effects of in leptin were compared with ip leptin in ad libitum fed rats.

RESULTS:

The in leptin increased CSF-IRL concentrations, although serum IRL concentrations of rats administered leptin in were lower than those administered ip The addition of 0.1 and 0.5% LPC dose-dependently increased serum IRL concentrations, but did not modify CSF-IRL concentrations in in leptin-treated rats. The in leptin inhibited dark-time food consumption at 0–1 h and 3–6 h in ad libitum fed rats. In contrast, ip leptin reduced food consumption only for an hour. Phosphorylated signal transducer and activator of transcription (STAT) 3 immunoreactive cells increased in the arcuate nucleus (ARC) of the hypothalamus at 3 h only following in leptin.

CONCLUSION:

The present study demonstrated that in leptin caused longer inhibition of appetite and phosphorylation of STAT3 in ARC. It is concluded that the trans-nasal route may be useful for the selective access of leptin to the brain in obese people.