Leptin and post-prandial satiety: acute central leptin more potently reduces meal frequency than meal size in the rat.
BACKGROUND
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.
Zorrilla
Eric P
EP
Department of Neuropharmacology, The Scripps Research Institute, 10550 N.Torrey Pines Rd., La Jolla, CA 92037, USA. ezorrilla@scripps.edu
Inoue
Koki
K
Valdez
Glenn R
GR
Tabarin
Antoine
A
Koob
George F
GF
D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects* / Q000502:physiology; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects / Q000502:physiology; D004435:Eating / Q000187:drug effects / Q000502:physiology; D005277:Fenfluramine / Q000008:administration & dosage / Q000493:pharmacokinetics; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D020738:Leptin / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D008297:Male; D019518:Postprandial Period / Q000187:drug effects* / Q000502:physiology; D011600:Psychopharmacology / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D012528:Satiety Response / Q000187:drug effects* / Q000502:physiology
D020738:Leptin; D005277:Fenfluramine