Leptin and post-prandial satiety: acute central leptin more potently reduces meal frequency than meal size in the rat.

RATIONALE: Many attempts to understand ingestion have sought to clarify the control of meals. Little is known about the effects of the anorexogenic hormone leptin on meal patterning.
OBJECTIVE: The present study sought to perform a dose-response analysis of the effects of acute central leptin administration on meal patterning using a validated, objective meal definition and to compare these results to those obtained with a previously used, subjective meal definition.
METHODS: To validate the objective meal definition pharmacologically, the microstructural effects of the well-studied compound fenfluramine (SC 0, 1, 2, 4 mg/kg) on spontaneous nocturnal intake were determined in mature, non-deprived male Wistar rats (n=8) using a full Latin square design. The effects of intracerebroventricular leptin administration (0, 0.3, 1, 3, 6.25 microg; n=10) were also examined, and perceived meal patterns obtained from the objective and subjective definitions were compared.
RESULTS: Fenfluramine reduced meal size and eating rate at doses that did not reduce meal frequency or duration. In contrast, comparably anorectic doses of leptin had potent post-meal satiety-like effects, reducing meal frequency and prolonging the intermeal interval without reducing average meal size, a finding opposite to that suggested by the previously used subjective meal definition. Unlike comparably and more anorectic doses of fenfluramine, leptin non-specifically reduced both prandial and non-prandial drinking.
CONCLUSIONS: Acute increases in central leptin levels may potently augment post-prandial satiety and influence body-fluid homeostasis. The results reveal unappreciated central modes of action for the ob protein which qualitatively differ from the intra-meal satiating-like effects of fenfluramine.