Leptin is a protein hormone originally identified from adipose tissue and known for its effects on appetite. Leptin is now known to be produced in many tissues including the stomach, and our earlier work showed that when a physiologic dose was injected intravenously approximately 13 % of the dose was recovered intact from the lumen of the gastrointestinal tract (GIT) after 60 minutes. To examine the pharmacokinetics of leptin in the GIT, non-fasted mice were lightly anaesthetised before oral gavage of 12 ng of 125I-labelled leptin. Samples were analysed by gel permeation HPLC to confirm that the leptin was not degraded and the amount present was determined using a γ-counter.
Radiolabelled leptin in the stomach declined from 53 % to 24 % of the administered dose 30 – 120 min post-gavage. A small peak (~ 4 – 8 % of the dose) appeared to move aborally through the small intestine, with approximately 4 % of the dose reaching the hindgut within the 2 h study. Throughout the experiment radiolabelled leptin was detected in the blood, with approximately 3.5 % of the dose calculated to be in the circulation at all times examined. The radiolabelled leptin in plasma was found to be 74 ± 6 % intact.
Here we show that leptin in the digestive tract moves aborally along the digestive tract, suggesting a role in the intestine. The gradual decline of leptin from the lumen of the stomach may indicate that leptin associates with digesta. We also report that leptin in the lumen of the gut was recovered intact from the blood. Our previous work has shown that leptin in the circulation is also recoverable from the lumen of the digestive tract, suggesting that leptin may be cycling between the gut and the circulation.