Leptin and post-prandial satiety: acute central leptin more potently reduces meal frequency than meal size in the rat
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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.
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.
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 μg; n=10) were also examined, and perceived meal patterns obtained from the objective and subjective definitions were compared.
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.
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.
KeywordsFood intake Water intake Obesity Satiation Appetite suppressant Anorectic drugs Food-associated drinking Serotonin Post-meal interval Meal pattern analysis
This study was supported by DK26741 and DK64871 from the National Institute of Diabetes and Digestive and Kidney Diseases (E.P.Z., G.F.K.). A.T. was supported by grants from the Fondation pour la Recherche Médicale and the Action Thématique Concertée “Nutrition” from INSERM. G.R.V. was supported by AA05563, an Individual National Research Service Award from the National Institute on Alcohol Abuse and Alcoholism. The authors thank Robert Lintz, Carmen Carrillo and Lindsay Reinhardt for technical contributions, and Mike Arends for editorial assistance. This is publication number 16298-NP from The Scripps Research Institute. The experiments comply with the current laws of the United States of America.
- Blevins JE, Knezetic J, Mackin R, Castellanos D, Reidelberger R (1996) Effects of intravenous and paraventricular nucleus injections of leptin on food intake in rats. Appetite 27:267Google Scholar
- Campbell DT, Kenny DA (1999) A primer on regression artifacts. Guilford, New YorkGoogle Scholar
- Clifton PG (1987) Analysis of feeding and drinking patterns. In Toates FM, Rowland NR (eds) Feeding and drinking. Elsevier, Amsterdam, pp 19–35Google Scholar
- Inoue K, Valdez GR, Reyes TM, Reinhardt LE, Tabarin A, Rivier J, Vale WW, Sawchenko PE, Koob GF, Zorrilla EP (2003) Human urocortin II, a selective agonist for the type 2 corticotropin-releasing factor receptor, decreases feeding and drinking in the rat. J Pharmacol Exp Ther 305:385–393CrossRefPubMedGoogle Scholar
- Johnson RF, Johnson AK (1997) The interaction of meal-related, rhythmic and homeostatic mechanisms and the generation of thirst and drinking. Brazil J Med Biol Res 30:487–491Google Scholar
- Montague CT, Farooqi IS, Whitehead JP, Soos MA, Rau H, Wareham NJ, Sewter CP, Digby JE, Mohammed SN, Hurst JA, Cheetham CH, Earley AR, Barnett AH, Prins JB, O’Rahilly S (1997) Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 387:903–908CrossRefPubMedGoogle Scholar
- Pellegrino LJ, Pellegrino AS, Cushman AJ (1979) A stereotaxic atlas of the rat brain. Plenum, New YorkGoogle Scholar