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      Impact of Meal Timing and Frequency on the Twenty-Four-Hour Leptin Rhythm

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          Abstract

          Objective: To study the influence of changes in meal timing and frequency on the diurnal rhythm of leptin and on the 24-hour profile of insulin and glucose. Patients and Methods: Five obese women were studied twice during a weight-maintaining diet in either 3 daily or 8 day and night equal portions. Blood was sampled for 24-hour profiles of leptin and insulin. Results: During the 8-meal intervention, the 24-hour rhythm of leptin changed significantly: the amplitude decreased (p = 0.0089) and the acrophase was delayed by 168 min (p = 0.021). Also, 8 small insulin secretion peaks occurred instead of the 3 postprandial high insulin peaks. Conclusion: The dispersion of food intake over 24 h affects the diurnal leptin rhythm. These changes could not be attributed to changes in circadian timing or energy balance. Instead, changes in daily insulin secretion profiles might play a role.

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          Most cited references12

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          Nocturnal rise of leptin in lean, obese, and non-insulin-dependent diabetes mellitus subjects.

          We studied 24-h profiles of circulating leptin levels using a sensitive and specific RIA in lean controls and obese subjects with or without non-insulin-dependent diabetes mellitus (NIDDM) during normal routine activity. Serum leptin levels were significantly higher in obese (41.7 +/- 9.0 ng/ml; n = 11) and obese NIDDM (30.8 +/- 6.7; n = 9) subjects compared with those in lean controls (12.0 +/- 4.4, n = 6). In all the three groups, serum leptin levels were highest between midnight and early morning hours and lowest around noon to midafternoon. The nocturnal rise in leptin levels was significant when data were analyzed by ANOVA (lean: F = 3.17, P 0.05) were observed between circulating levels of leptin and either insulin or glucose levels in any of the 20 subjects studied for 24-h profiles. The nocturnal rise in leptin observed in the present study resembles those reported for prolactin, thyroid-stimulating hormone, and free fatty acids. We speculate that the nocturnal rise in leptin could have an effect in suppressing appetite during the night while sleeping.
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            Nibbling versus gorging: metabolic advantages of increased meal frequency.

            We studied the effect of increasing the frequency of meals on serum lipid concentrations and carbohydrate tolerance in normal subjects. Seven men were assigned in random order to two metabolically identical diets. One diet consisted of 17 snacks per day (the nibbling diet), and the other of three meals per day (the three-meal diet); each diet was followed for two weeks. As compared with the three-meal diet, the nibbling diet reduced fasting serum concentrations of total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B by a mean (+/- SE) of 8.5 +/- 2.5 percent (P less than 0.02), 13.5 +/- 3.4 percent (P less than 0.01), and 15.1 +/- 5.7 percent (P less than 0.05), respectively. Although the mean blood glucose level and serum concentrations of free fatty acids, 3-hydroxybutyrate, and triglyceride were similar during both diets, during the nibbling diet the mean serum insulin level decreased by 27.9 +/- 6.3 percent (P less than 0.01) and the mean 24-hour urinary C-peptide output decreased by 20.2 +/- 5.6 percent (P less than 0.02). In addition, the mean 24-hour urinary cortisol excretion was lower by 17.3 +/- 5.9 percent (P less than 0.05) at the end of the nibbling diet than at the end of the three-meal diet. The blood glucose, serum insulin, and C-peptide responses to a standardized breakfast and the results of an intravenous glucose-tolerance test conducted at the end of each diet were similar. We conclude that in addition to the amount and type of food eaten, the frequency of meals may be an important determinant of fasting serum lipid levels, possibly in relation to changes in insulin secretion.
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              Entrainment of the diurnal rhythm of plasma leptin to meal timing.

              To identify the physiologic factor(s) that entrain the diurnal rhythm of plasma leptin, leptin levels were measured hourly after changes in light/dark cycle, sleep/wake cycle, and meal timing. Four young male subjects were studied during each of two protocols, those being a simulated 12-h time zone shift and a 6.5-h meal shift. During the baseline day, plasma leptin demonstrated a strong diurnal rhythm with an amplitude of 21%, zenith at 2400 h, and nadir between 0900 and 1200 h. Acute sleep deprivation did not alter plasma leptin, but day/night reversal (time zone shift) caused a 12+/-2 h shift (P < 0.01) in the timing of the zenith and nadir. When meals were shifted 6.5 h without changing the light or sleep cycles, the plasma leptin rhythm was shifted by 5-7 h (P < 0.01). The phase change occurred rapidly when compared with changes in the diurnal rhythm of cortisol, suggesting that leptin levels are not acutely entrained to the circadian clock. The leptin rhythm was altered by meal timing in a manner very similar to the rhythm of de novo cholesterol synthesis. We conclude that the diurnal rhythm of plasma leptin in young males is entrained to meal timing.
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                Author and article information

                Journal
                HRE
                Horm Res Paediatr
                10.1159/issn.1663-2818
                Hormone Research in Paediatrics
                S. Karger AG
                1663-2818
                1663-2826
                2004
                September 2004
                13 September 2004
                : 62
                : 2
                : 71-78
                Affiliations
                Departments of aGeneral Internal Medicine and bClinical Chemistry, Leiden University Medical Center, Leiden, TheNetherlands
                Article
                79326 Horm Res 2004;62:71–78
                10.1159/000079326
                15218336
                dfb24c65-aa9d-40e6-bac4-7e6d33ca6409
                © 2004 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 28 November 2003
                : 20 April 2004
                Page count
                Figures: 3, Tables: 4, References: 26, Pages: 8
                Categories
                Original Paper

                Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Tenty-four-hour leptin rhythm,Diurnal leptin rhythm

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