Determination of the half-life of circulating leptin in the mouse.

BACKGROUND: The adipokine hormone, leptin, is a major component of body weight homeostasis. Numerous studies have been performed administering recombinant mouse leptin as an experimental reagent; however, the half-life of circulating leptin following exogenous administration of recombinant mouse leptin has not been carefully evaluated. METHODS: Exogenous leptin was administered (3 mg leptin per kg body weight) to 10-week-old fasted non-obese male mice and plasma was serially collected at seven time points; plasma leptin concentration was measured by enzyme-linked immunosorbent assay at each time point to estimate the circulating half-life of mouse leptin. RESULTS: Under the physiological circumstances tested, the half-life of mouse leptin was 40.2 (±2.2) min. Circulating leptin concentrations up to 1 h following exogenous leptin administration were 170-fold higher than endogenous levels at fasting. CONCLUSIONS: The half-life of mouse leptin was determined to be 40.2 min. These results should be useful in planning and interpreting experiments employing exogenous leptin. The unphysiological elevations in circulating leptin resulting from widely used dosing regimens for exogenous leptin are likely to confound inferences regarding some aspects of the hormone's clinical biology.

Effects of chronic leptin infusion on subsequent body weight and composition in mice: Can body weight set point be reset?

Circulating leptin concentrations correlate with fat mass and signal the status of somatic energy stores to the brain. Previous studies suggest that diet-induced elevations of body weight increase body weight "set-point". To assess whether chronic hyperleptinemia is responsible for this shift in defended body weight, we elevated circulating leptin concentrations in lean mice to those comparable to diet-induced obese mice for eighteen weeks. We hypothesized that following cessation of leptin infusion, a higher body weight would be defended. Compared to saline-infused controls, leptin-infused mice had elevated circulating leptin concentrations, gained less weight, yet had similar metabolic rates. Following cessation of leptin administration, leptin-infused mice gained some weight yet plateaued at 5-10% below controls. These results suggest that, unlike mice rendered hyperleptinemic by diet-induced weight gain, leptin-infused mice do not subsequently "defend" a higher body weight, suggesting that hyperleptinemia per se does not mimic the CNS consequences of chronic weight gain.

Children's processing of prosodic cues for phrasal interpretation.

Using synthetic speech, word duration and fundamental frequency (F0) contours were parametrically manipulated to examine processes of phrasal interpretation by adult and child (5 and 7 years old) listeners. From an adult male voice, versions of the phrase "pink and green and white" were resynthesized to produce stimuli suggesting two possible interpretations: [(pink and green) and white] and [pink and (green and white)]. For each stimulus, listeners pointed to a picture to indicate which interpretation was intended. All subjects used duration and (to a lesser extent) intonation as perceptually salient cues for phrasal interpretation. The manner in which subjects processed this information was evaluated by comparing subjects' performance with the predictions of three different information processing models: a nonindependent cue-evaluation model, and two independent cue-evaluation models (an additive model, and the multiplicative, fuzzy logical model). Performance was best described by the fuzzy logical model, which assumes independent cue evaluation and generates a classification function characterized by cue trading relations. The results suggest that, similar to adults, children as young as 5 years of age rely on acoustic-prosodic information for syntactic phrase interpretation, and they process this information in an adultlike manner.