Leptin pharmacokinetics in male mice

Abstract

Pharmacokinetics of leptin in mammals has not been studied in detail and only one study has examined more than one time point in non-mutant mice and this was in a female mice. This is the first study to describe leptin distribution over a detailed time course in normal male mice. A physiologic dose (12 ng) of radiolabelled leptin was injected into adult male mice via the lateral tail vein and tissues were dissected out and measured for radioactivity over a time course of up to two hours. Major targets were the digestive tract, kidneys, skin and lungs. The brain was not a major target, and 0.15% of the total dose was recovered from the brain 5 min after administration. Major differences appear to exist in the distribution of leptin between the male and female mice, indicating a high degree of sexual dimorphism. Although the half-lives were similar between male and female mice, almost twice the proportion of leptin was recovered from the digestive tract of male mice in comparison to that reported previously for females. This would seem to indicate a major difference in leptin distribution and possibly function between males and females.

Keywords: dimorphism; gastrointestinal tract; leptin; mice; pharmacokinetics.

Figure 1

Major targets for administered radiolabelled leptin in male mice measured as percentage of dose (GI Tract – gastrointestinal tract and contents; Other tissues – pooled data for testes, epididymides, seminal vesicles, epididymal fat, heart, lungs and brain).

Figure 2

Plasma clearance of intravenously administered radiolabelled leptin in male mice with a second-order exponential decay curve fit.

Figure 3

Radiolabelled leptin recovered per gram of tissue from male mice (A – kidneys; B – lungs; C – muscle; D – liver; E – skin; F – brain).