Moderate physical activity permits acute coupling between serum leptin and appetite–satiety measures in obese women

Article metrics

Abstract

OBJECTIVES: To investigate whether moderate physical activity or snack intake influence appetite sensations and subsequent food intake in obese women. Associations between serum leptin and appetite ratings were also investigated.

METHODS: In all, 10 obese women (mean age±s.d.: 50.0±8.5 y; mean body mass index (BMI)±s.d.: 37.2±6.5 kg m−2) were submitted in random order to three trials: Moderate physical activity (20 min brisk walking), Snack (58.5 g chocolate-based) and Control (sitting, TV-watching). Appetite and satiety were assessed by visual analogue scales, and serum leptin, blood glucose and plasma free fatty acids were measured at baseline, pre- and postintervention and 1 h postintervention (ie, before dinner). A buffet-style dinner was provided subsequent to the three trials.

RESULTS: The moderate physical activity and snack intake both produced lower appetite and higher satiety and fullness perceptions, compared to control, following the intervention. No significant differences were found in subsequent food intake. Serum leptin concentrations did not differ between trials. Serum leptin was not associated with appetite or satiety sensations at any time during the control or the snack trials, but was correlated following moderate physical activity (prospective food consumption rs=−0.83, P=0.003; hunger rs=−0.79, P=0.007; desire to eat rs=−0.69, P=0.02; satiety rs=0.71, P=0.02; fullness rs=0.66, P=0.04). These associations were not influenced by BMI or fat mass.

CONCLUSIONS: Moderate physical activity and snack intake suppress the appetite of obese women acutely. The associations between circulating leptin and appetite–satiety ratings suggest leptin involvement in short-term appetite regulation in response to physical activity-induced factors.

Introduction

A physiological function for leptin in appetite regulation is supported by findings both in mouse and man. Animal studies have demonstrated that administration of leptin, either peripherally or centrally, reduces food intake and body mass in congenitally obese leptin-deficient ob/ob mice but not in mice with mutations in the ob-receptor (db/db mice).1 In humans, obese patients with ob-gene or ob-receptor mutations are severely obese and hyperphagic,1 and leptin-deficient children are reported to respond to treatment with leptin.2 However, the role of leptin in common obesity (without ob-gene or ob-receptor abnormalities) is unclear. Appetite regulation involves interactions of many psychobiological systems.3 Leptin is only a part of a complex peripheral and central circuit and probably not a dominant one in the fed state although it may become more important during starvation.4

Obese individuals have high circulating leptin concentrations, suggesting normal leptin synthesis and secretion,5 but show weak appetite control during the process of weight gain. As such, obese individuals show little or no response to exogenous leptin administration6 and have therefore been considered ‘leptin resistant’.7 Other factors must therefore explain the ‘uncoupling’ of leptin to appetite in obese individuals. As the increase in obesity in recent years is linked to an excessive food intake relative to a reduced physical activity,8,9 overeating and inactivity may therefore be responsible, in part at least, for this ‘uncoupling’ of leptin to appetite.

Previous studies have used several eating or diet and exercise interventions in an attempt to induce changes in circulating leptin concentrations to investigate the link between serum leptin and appetite regulation.10,11,12,13,14,15,16,17,18,19,20,21,22,23 These studies found no relationship between circulating leptin concentrations and appetite sensations acutely after a meal in normal weight or obese individuals16,17 or during 20 min food exposure in obese individuals.18 Serum leptin was found to correlate with appetite sensations only during weight loss or maintenance induced by diet and exercise in obese individuals.14,16,19 As such, leptin has been considered as a long-term regulator of appetite during prolonged energy deficits where, presumably, signals increased appetite and food intake to restore fat loss. However, many studies have reported that mixed or carbohydrate-rich meals increase serum leptin concentrations,10,12,13,15,21,22 indicating that food intake regulates leptin secretion in the short-term. Fasting for 52–72 h has also been found to decrease leptin concentration, while an increase in circulating leptin was reported after overfeeding (12 h) without marked weight changes in normal weight and obese individuals.11,20,23 Moreover, acute exercise interventions have involved high-intensity exercise and examined only the effects of exercise on leptin synthesis and/or secretion in normal weight or overweight men.24,25,26,27,28

The purpose of the present study, therefore, was to investigate the effects of more moderate physical activity and eating interventions, similar to those encountered in normal living, on short-term appetite sensations. This was achieved by investigating the effect of moderate physical activity in the form of brisk walking and a modest snack on appetite sensations and on subsequent food intake in obese women. The association between serum leptin concentration and appetite sensations after moderate physical activity and snack was also investigated.

Methods

Subjects

In all, 10 obese but otherwise healthy women (Table 1) gave their written informed consent to take part in the study, which was approved by the Glasgow Royal Infirmary Research Ethics Committee. Of the 10 women, five were pre- and five were postmenopausal. All subjects were in good physical and mental health, nonsmokers, not on any medication known to affect appetite, not known to be anaemic or hyperlipidaemic and not on a special diet.

Table 1 Subject characteristics, n=10

Experimental design and protocol

Subjects were first familiarised with the appetite questionnaire29 and kept food and physical activity records for 2 days preceding the first experimental trial and up to arrival at the laboratory. These food and activity patterns were replicated before subsequent trials. Household measures (ie, glasses, cupfuls, tablespoons, slices, etc) were used to quantify food and drink consumption.

Subjects took part in three experimental trials: Moderate physical activity, Snack and Control. The order of the three trials was randomised across subjects in a counterbalanced Latin-square design. There was an interval of at least 2 days between trials, and all trials were performed within 2 weeks for each subject. The study design is represented diagrammatically in Figure 1. On each of the three study days, subjects visited the laboratory approximately 2.5 h after having consumed a standard lunch. Upon arrival at the laboratory, body mass and height were recorded and percentage body fat and fat-free mass were measured using a Bodystat-1500 Bioimpedance analyser (Bodystat Ltd., Isle of Man).30 Following this, subjects rested in a seated position for 10 min, and a baseline, venous blood sample (−60 min) was then taken. The cannula was kept patent by a slow (ca. 0.5 ml min−1) infusion of isotonic saline. Serial blood samples (10 ml) were drawn at 0, 30 and 90 min. Subjects remained seated and relaxed for at least 10 min prior to each blood sample. A set of self-rating 100-mm visual analogue scales for hunger, desire to eat, prospective food consumption, satiety and fullness29 was completed after each blood sample. Within-subject comparisons are suggested to provide the best use of visual analogue scales, eliminating the intersubject variation in appetite response.31

Figure 1
figure1

Schematic representation of the study design.

Throughout each trial, subjects were seated in a comfortable environment and watched food-related videotapes for the first hour. For each trial, there was a set of videotapes demonstrating recipes of appetizing foods. Food-related videotapes were intended to direct participants attention towards food and eating, to stimulate a familiar form of home entertainment that might distract subjects and reduce eating restraint.32 Subjects were required to remain seated for 30 min (Control trial) or were served a Snack (58.5 g chocolate-based snack: 1189 kJ (284 kcal), 36.0 g carbohydrate, 13.6 g fat, 4.6 g protein) and asked to consume it within 20 min while remaining seated (snack trial) or were asked to walk at a brisk pace for 20 min (Moderate physical activity trial). The television was switched off for 30 min during each intervention. Following each intervention, subjects continued to watch food-related videotapes for another 1 h. Subjects were then served a buffet-type dinner comprising 10 food items. At dinner, subjects were asked to eat as much as they wanted within 1 h. Subjects ate alone and nonsupervised during the buffet dinner because the number of people present at a meal has been established to influence the amount eaten in a meal.33 All food items were weighed before eating, and the leftovers were weighed again at the end of the dinner. Each subject's selection from the buffet dinner was analysed for energy intake and macronutrient content using a computerised version of McCance and Widdowson's food composition tables.34 Water was provided upon request at the first trial and subjects were asked to replicate the amount drunk during the following two trials. Prior to the study, subjects were asked about food likes and dislikes to define the snack and the buffet meal, which all subjects would like.

The brisk walking was performed indoors under supervision in the Clinical Investigation Unit of the Department of Human Nutrition. Heart rate was measured (Polar Sport Tester, Polar Electro OY, Kempele, Finland) and ratings of perceived exertion (RPE)35 recorded separately for breathlessness and leg exertion at 5 min intervals during the exercise. Subjects were instructed to maintain a level of exertion of approximately 13 on the RPE scale (ie, corresponding to ‘somewhat hard’). Heart rate at rest and at the end of the moderate physical activity intervention was 80±6 and 123±18 b min−1, respectively (mean±s.d.). Subjective perceived exertion was somewhat hard (14±2) at the end of the moderate physical activity.

Blood treatment and analyses

Venous blood was collected into K3EDTA vacutainers for the measurement of blood glucose and plasma-free fatty acids (FFA) and into clot activator vacutainers for serum leptin measurement. Duplicate aliquots (400 μl) of whole blood from the K3EDTA tube were rapidly deproteinised in 800 μl of ice-cold 0.3 mol l−1 perchloric acid; following centrifugation, the supernatant was used for the measurement of glucose.36 The remaining plasma supernatant was separated and stored at −20°C and later used for the measurement of FFA (colorimetric method, Boehringer Mannheim Biochemica, London, UK). Blood collected into the clot activator vacutainer was allowed to clot for 10 min. Following centrifugation, the serum was stored at −70°C and subsequently analysed for leptin by radioimmunoassay.37

Statistical analyses

Data are expressed as mean±s.d. or median (range) as appropriate following a test for normality of distribution. Data describing serum leptin concentrations and appetite–satiety ratings were not normally distributed, so all comparisons of responses to the three interventions were made using nonparametric tests. The Kruskal–Wallis test was performed to determine at which time points there were treatment effects. Post hoc analysis by the Wilcoxon signed-rank test was performed to determine treatment difference at each time point and effects over time within each treatment. Correlation analysis between serum leptin and appetite measures (for each time point separately) and adiposity indices was carried out using the Spearman rank correlation coefficient (rs). Statistical significance was taken as P<0.05.

Results

Effects on self-reported appetite–satiety measures and subsequent dietary intake

Profiles of hunger, desire to eat, prospective food consumption, fullness and satiety throughout each trial are shown in Figure 2. The moderate physical activity and snack interventions both induced significantly higher perceptions of satiety and fullness compared to control; ratings were significantly higher compared to control immediately after the moderate physical activity (P=0.01 satiety; P=0.02 fullness) and snack intervention (30 min) (P=0.01 satiety; P=0.01 fullness). Only in the moderate physical activity trial was satiety still significantly higher 1 h after the intervention (90 min) compared to control (P=0.02). Significant suppression of hunger was found immediately after the snack intervention (30 min) compared to control (P=0.01) and moderate physical activity (P=0.03). Desire to eat and prospective food consumption were significantly lower immediately after the snack intervention (30 min) compared to control (P=0.01 desire to eat; P=0.01 prospective food consumption), but only desire to eat was still suppressed 1 h after the snack intervention (90 min) (P=0.01). Desire to eat and prospective food consumption were also significantly lower immediately after the moderate physical activity intervention (30 min) compared to control (P=0.03 desire to eat; P=0.009 prospective food consumption).

Figure 2
figure2

Median profiles of self-reported appetite–satiety ratings under the Moderate physical activity (▪), Snack () and Control (•) trials; data were analysed using Kruskal–Wallis test followed by Wilcoxon-signed rank test to determine the differences in ratings between trials. *, †, ‡ indicate significant differences between trials, P<0.05 (*Moderate physical activity vs Control; Snack vs Moderate physical activity; Snack vs Control); §** are significantly different from baseline within the Moderate physical activity (§P<0.05), the Snack (P<0.05) or the Control (**P≤0.01) trial. The range has been excluded for clarity reasons.

Self-selected food intake at dinner did not differ significantly between trials (2860 (2134–4234 kJ) Moderate physical activity, 2751 (2268–3108 kJ) Snack, 3032 (2134–5733 kJ) Control; protein 67.1 (38.4–79.9) g Moderate physical activity, 54.9 (41.3–70.8) g Snack, 59.7 (35.3–96.2) g Control; carbohydrate 59.7 (49.8–103.8) g Moderate physical activity, 65.3 (34.7–75.6) g Snack, 76.9 (45.0–138.6) g Control; fat 19.6 (6.5–32.7) g Moderate physical activity, 23.9 (13.2–30.3) g Snack, 25.7 (12.6–51.4) g Control), median (range).

Effects on biochemical measures

Serum leptin, blood glucose and plasma FFA concentrations during the three trial conditions are shown in Table 2. There was no significant effect of any intervention or effect over time on serum leptin concentrations (P>0.05). Significant differences between trials were found in blood glucose and plasma FFA concentrations after the moderate physical activity and snack interventions. Snack intake induced significantly higher glucose concentrations immediately after the snack intervention (30 min) compared to control or moderate physical activity trial (P=0.009). At 1 h after the snack intervention (90 min), glucose concentrations were still higher in the snack trial than in the control (P=0.02) or moderate physical activity trial (P=0.02), whereas plasma FFA concentrations were significantly lower in the snack trial compared to the control and the moderate physical activity trial (P=0.009). The moderate physical activity intervention induced higher plasma FFA concentrations immediately after intervention (30 min) compared to both the control and the snack trial (P=0.009). Significant time effect for glucose and FFA concentrations was found in the moderate physical activity and snack trials.

Table 2 Serum leptin, blood glucose and plasma free fatty acid (FFA) concentrations during the Control, Moderate physical activity and Snack trials

No significant associations were demonstrated between serum leptin and blood glucose or plasma FFA concentrations at any time point in the three trials (P>0.05). Baseline serum leptin concentrations correlated significantly with body mass index (BMI (kg m−2)) and fat mass (FM (kg)) in all trials (BMI rs=0.73, P=0.02, FM rs=0.88, P=0.001 Moderate physical activity; BMI rs=0.69, P=0.02, FM rs=0.85, P=0.002 Snack; BMI rs=0.78, P=0.008, FM rs=0.90, P<0.001 Control).

Correlations between biochemical measures and self-reported appetite–satiety measures

No significant correlations were found between serum leptin and appetite or satiety ratings at any time in the control or the snack trial. Only in the moderate physical activity trial was serum leptin concentration significantly correlated with prospective food consumption immediately after intervention (30 min) (rs=−0.83, P=0.003). Additionally, 1 h after the moderate physical activity intervention (90 min), serum leptin concentrations were significantly correlated with appetite or satiety ratings (hunger rs=−0.79, P=0.007; desire to eat rs=−0.69, P=0.02; satiety rs=0.71, P=0.02; fullness rs=0.66, P=0.04) (Figure 3). The associations between leptin and appetite–satiety ratings found immediately after and 1 h after the moderate physical activity intervention remained significant when circulating leptin concentrations were adjusted for adiposity by dividing by BMI (30 min hunger rs=−0.75, P=0.01; desire to eat rs=−0.75, P=0.01; prospective food consumption rs=−0.86, P=0.002; 90 min hunger rs=−0.74, P=0.01; satiety rs=0.67, P=0.03; fullness rs=0.66, P=0.04). The associations also remained significant when serum leptin concentrations were adjusted for fat mass (30 min hunger rs=−0.71, P=0.02; desire to eat rs=−0.71, P=0.02; prospective food consumption rs=−0.84, P=0.002; 90 min hunger rs=−0.74, P=0.01; satiety rs=0.67, P=0.03; fullness rs=0.66, P=0.04).

Figure 3
figure3

Associations between serum leptin concentrations (ng ml−1, ranked) and appetite–satiety measures (on a 0–100-mm scale, ranked) in the physical activity trial 1 h after the moderate physical activity intervention (hunger (rs=−0.79, P=0.007); desire to eat (rs=−0.69, P=0.02); satiety (rs=0.71, P=0.02); fullness (rs=0.66, P=0.04)).

Discussion

The study used brisk walking and a chocolate-based snack, in an attempt to replicate typical physical activity and eating behaviours, to investigate the effects on appetite and on associations between serum leptin and appetite. Associations between circulating leptin and suppressed appetite or elevated satiety were found following a bout of moderate physical activity, but not at any time point during the snack or the control conditions.

In other studies of leptin and appetite, circulating leptin concentrations have been associated with appetite or fullness perceptions, but only in fasting obese or postobese individuals and during weight loss or maintenance produced by diet or diet and aerobic exercise.14,16,19 These observations support the view that leptin regulates appetite centrally only after sustained fat loss to re-establish fat homeostasis in fat tissue.38 In contrast, during the process of weight gain, high serum leptin concentrations are closely related to body fat,5 but are not usually coupled with appetite suppression in obese individuals. Therefore, serum leptin has not been considered to play a role in short-term appetite processes, or there is possibly some form of ‘resistance’ to short-term central actions of leptin in human obesity. However, the present study indicates that circulating leptin may indeed be involved in short-term appetite regulation in obese individuals but only after physical activity. Therefore, physical activity-induced factor(s) may be responsible for the observed ‘coupling’ of leptin to appetite.

The moderate physical activity employed in the present study, as expected, did not affect circulating leptin concentrations. Only extreme exercise (2–3.5 h marathon running, 2 h of strenuous cycling) is known to decrease plasma leptin concentrations.24,25,26 It is likely that physical activity could influence leptin transport into the brain, which could explain the ‘coupling’ of leptin to appetite found after a bout of moderate-intensity physical activity. Some studies have suggested impaired leptin transport across the blood–brain barrier in animals39 and probably in humans7 residing in an ‘obesigenic’ environment (ie, increased food intake and/or physical inactivity). This reduced transport of leptin into the brain is proposed as a possible mechanism for leptin ‘resistance’ in obesity. An exercise effect on leptin transport into the brain has not been investigated in humans, but animal findings indicate enhanced leptin transport into the brain mediated by elevated circulating adrenaline concentrations.40 Plasma catecholamines were not measured in the present study. However, increased plasma FFA concentrations were found after the moderate physical activity (average FFA 1.2 mmol l−1), which is indicative of adrenaline-stimulated lipolysis.41 Catecholamines have been recognised as important modulators of leptin production and secretion,42,43 but whether they could regulate leptin uptake into the brain in humans is unknown. If catecholamines are responsible for the ‘coupling’ of circulating leptin to satiety following moderate physical activity, then this begins to unravel a mechanism by which physical activity-induced factors may influence appetite by enhancing leptin transport into the brain. Leptin has been suggested to have a particular function in the hunger drive under starvation conditions,44 but may have a more extended physiological role. It is possible that individuals predisposed to obesity may need greater physical activity than others, in order for serum leptin to be transported into the brain efficiently and curtail appetite.

Circulating catecholamine concentrations are also increased after carbohydrate-rich meals in parallel with serum leptin concentrations,21,45,46 and a positive association has been found between the elevated circulating leptin and catecholamine concentrations after a carbohydrate-rich diet.21 Food intake, and predominantly carbohydrate intake, stimulates leptin secretion,10,12,13,15,21,22 but no association has been found between the increased serum leptin concentrations and the heightened postprandial satiety in the short term (up to 9 h postprandially) in lean or postobese individuals.21,22

In the context of weight management for obesity, physical activity or exercise alone are better linked with weight maintenance than with enhanced weight reduction.47,48 The present results indicated very consistently that obese individuals who engage in 20 min of moderate physical activity during the course of the day could improve acute appetite control and avoid the caloric burden of snacking. The numbers in the current study were small increasing the chance of type 2 errors but there was no previous source of bias, which might confound these results. Baseline measures of appetite and satiety sensations and of biochemical variables were not different between subjects in the three trial conditions. This indicates subjects adherence to instructions to standardise diet and physical activity for 2 days prior to each study day. The consumption of a modest snack (1189 kJ) produced lower feelings of appetite and higher satiety-fullness perceptions, as expected, but did not decrease subsequent food intake. Similarly, a short bout of brisk walking, equivalent to approximately 502 kJ energy cost, increased satiety-fullness perceptions transiently, and most importantly did not increase the subsequent food intake. Moderate-intensity physical activities can be adopted by obese individuals to promote satiety and are more likely to be continued than high-intensity physical activities.49

The present study assessed appetite and satiety in relation to snacking or moderate physical activity in the afternoon and evening. Most previous research has been conducted with the morning fasting state as baseline, but it is in the afternoon or evening that most obese individuals tend to report higher food intake.50 Snack intake did not decrease the subsequent food intake, and serum leptin concentrations in accordance with previous studies16,17,22 were not associated with post-snack satiety ratings. Hence, circulating leptin concentrations do not appear to be primary regulators of short-term satiety following a meal. The observations that moderate physical activity can suppress appetite without increasing subsequent food intake supports the view that the apparent urge to eat, experienced by obese women, may be a misinterpreted signal of boredom while physically inactive. However, studies in normal weight individuals are needed to explore this possibility. The present results suggest that moderate physical activity could be used to prolong meal-induced satiety and suppress the drive to eat during the early postprandial phase, that is, the period of ‘readiness to eat’. ‘Readiness to eat’ appears to be resumed soon after meal cessation, when there is still relative satiation and before appetite has developed.

The results of the present study extend our understanding of the role of moderate physical activity in appetite regulation and obesity prevention. Physical activity may have a permissive role, allowing effective signalling from a high leptin concentration to curtail appetite. This could explain, firstly, the paradoxical finding of deregulation of appetite during chronic inactivity.51 Secondly, it provides a mechanism as to why inactivity (ie, watching television, often in the afternoon and/or evening) is having such pervasive effects on appetite and body weight regulation,9 possibly by an ‘uncoupling’ of circulating leptin to appetite control. Additionally, the present findings may offer an explanation for the disappointing results in clinical trials with recombinant human leptin administration, which alone, provides little benefit in obesity treatment.52

References

  1. 1

    Friedman JM, Halaas JL . Leptin and the regulation of body weight in mammals. Nature 1998; 395: 765–770.

  2. 2

    Farooqi IS, Jebb SA, Langmack G, Lawrence E, Cheetham CH, Prentice AM, Hughes IA, McCamish MA, O'Rahilly S . Effects of recombinant leptin therapy in a child with recombinant leptin deficiency. N Engl J Med 1999; 341: 879–884.

  3. 3

    Blundell JE, Goodson S, Halford JCG . Regulation of appetite: role of leptin in signalling systems for drive and satiety. Int J Obes Relat Metab Disord 2001; 25: S29–S34.

  4. 4

    Ahima RS, Prabakaran D, Mantzoros C, Qu D, Lowell B, Maratos-Flier E, Flier JS . Role of leptin in the neuroendocrine response to fasting. Nature 1996; 382: 250–252.

  5. 5

    Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ, Bauer TL, José F Caro . Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 1996; 334: 292–295.

  6. 6

    Mantzoros CS, Flier JS . Editorial: leptin as a therapeutic agent–trials and tribulations. J Clin Endocrinol Metab 2000; 85: 4000–4002.

  7. 7

    Caro JF, Kolaczynski JW, Nyce MR, Ohannesian JP, Opentanova I, Goldman WH, Lynn RB, Zhang PL, Sinha MK, Considine RV . Decreased cerebrospinal fluid/serum leptin ratio in obesity: a possible mechanism for leptin resistance. Lancet 1996; 348: 159–161.

  8. 8

    Prentice AM, Jebb SA . Obesity in Britain: gluttony or sloth? Br Med J 1995; 311: 437–439.

  9. 9

    Dietz WH . The obesity epidemic in young children: reduce television viewing and promote playing. Br Med J 2001; 322: 313–314.

  10. 10

    Astrup A, Ranneries C, Simonsen L, Bulow J, Friedman J . Leptin: a short-term acting glucostatic hormone? Int J Obes Relat Metab Disord 1997; 21: S13.

  11. 11

    Boden G, Chen X, Mozzoli M, Ryan I . Effect of fasting on serum leptin in normal human subjects. J Clin Endocrinol Metab 1996; 81: 3419–3423.

  12. 12

    Caixas A, Bashore C, Nash W, Pi-Sunyer F, Laferrere B . Insulin, unlike food intake, does not suppress ghrelin in human subjects. J Clin Endocrinol Metab 2002; 87: 1902–1906.

  13. 13

    Dallongeville J, Hecquet B, Lebel P, Edme JL, Le Fur C, Fruchart JC, Auwerx J, Romon M . Short term response of circulating leptin to feeding and fasting in man: influence of circadian cycle. Int J Obes Relat Metab Disord 1998; 22: 728–733.

  14. 14

    Doucet E, Imbeault P, St-Pierre S, Almeras N, Mauriege P, Richard D, Tremblay A . Appetite after weight loss by energy restriction and low-fat diet-exercise follow up. Int J Obes Relat Metab Disord 2000; 24: 906–914.

  15. 15

    Evans K, Clark ML, Frayn KN . Carbohydrate and fat have different effects on plasma leptin concentrations and adipose tissue leptin production. Clin Sci 2001; 100: 493–498.

  16. 16

    Heini AF, Lara-Castro C, Kirk KA, Considine RV, Caro JF, Weinsier RL . Association of leptin and hunger–satiety ratings in obese women. Int J Obes Relat Metab Disord 1998; 22: 1084–1087.

  17. 17

    Joannic JL, Oppert JM, Lahlou N, Basdevant A, Auboiron S, Raison J, Bornet F, Guy-Grand B . Plasma leptin and hunger ratings in healthy humans. Appetite 1998; 30: 129–138.

  18. 18

    Karhunen L, Haffner S, Turpeinen A, Miettinen H, Uusitupa M . Serum leptin and short-term regulation of eating in obese women. Clin Sci 1997; 92: 573–578.

  19. 19

    Keim NL, Stern JS, Havel PJ . Relation between circulating leptin concentrations and appetite during a prolonged, moderate energy deficit in women. Am J Clin Nutr 1998; 68: 794–801.

  20. 20

    Kolaczynski JW, Ohannesian JP, Considine RV, Marco CC, Caro JF . Response of leptin to short-term and prolonged overfeeding in humans. J Clin Endocrinol Metab 1996; 81: 4162–4165.

  21. 21

    Raben A, Astrup A . Leptin is influenced both by predisposition to obesity and diet composition. Int J Obes Relat Metab Disord 2000; 24: 450–459.

  22. 22

    Romon M, Lebel P, Velly C, Marecaux N, Fruchart JC, Dallongeville J . Leptin response to carbohydrate or fat meal and association with subsequent satiety and energy intake. Am J Physiol 1999; 277: E855–E861.

  23. 23

    Weigle DS, Duell PB, Connor WE, Steiner RA, Soules MR, Kuijper JL . Effect of fasting, refeeding, and dietary fat restriction in plasma leptin levels. J Clin Endocrinol Metab 1996; 82: 561–565.

  24. 24

    Duclos M, Corcuff JB, Ruffie A, Roger P, Manier G . Rapid leptin decrease in immediate post-exercise recovery. Clin Endocrinol 1999; 50: 337–342.

  25. 25

    Landt M, Lawson GM, Helgeson JM, Davila-Roman VG, Ladenson JH, Jaffe AS, Hickner RC . Prolonged exercise decreases serum leptin concentrations. Metabolism 1997; 46: 1109–1112.

  26. 26

    Leal-Cerro A, Garcia-Luna PP, Astorga R, Parejo J, Peino R, Dieguez C, Casanueva FF . Serum leptin levels in marathon athletes before and after the marathon run. J Clin Endocrinol Metab 1998; 83: 2376–2379.

  27. 27

    Perusse L, Collier G, Gagnon J, Leon AS, Rao DC, Skinner JS, Wilmore JH, Nadeau A, Zimmet PZ, Bouchard C . Acute and chronic effects of exercise on leptin levels in humans. J Appl Physiol 1997; 83: 5–10.

  28. 28

    Racette SB, Coppack S, Landt M, Klein S . Leptin production during moderate-intensity aerobic exercise. J Clin Endocrinol Metab 1997; 82: 2275–2277.

  29. 29

    Flint A, Raben A, Blundell JE, Astrup A . Reproducibility, power and validity of visual analogue scales in assessment of appetite sensations in single test meal studies. Int J Obes Relat Metab Disord 2000; 24: 38–48.

  30. 30

    Kushner RF, Schoeller DA . Estimation of total body water by bioelectrical impedance analysis. Am J Clin Nutr 1986; 44: 417–424.

  31. 31

    Stubbs RJ, Hughes DA, Johnstone AM, Rowley E, Reid C, Elia M, Stratton R, Delargy H, King N, Blundell JE . The use of visual analogue scales to assess motivation to eat in human subjects: a review of their reliability and validity with an evaluation of new hand-held computerized systems for temporal tracking of appetite ratings. Br J Nutr 2000; 84: 405–415.

  32. 32

    Bellisle F, Dalix AM . Cognitive restraint can be offset by destruction, leading to increased meal intake in women. Am J Clin Nutr 2001; 74: 197–200.

  33. 33

    de Castro JM . Eating behavior: lessons from the real world of humans. Nutrition 2000; 16: 800–813.

  34. 34

    Holland B, Welch AA, Unwin ID, Buss DH, Paul AA, Southgate DAT . McCance and Widdowson's The composition of foods, 5th edn Goodfellow & Egan Phototypesetting Ltd: Cambridge; 1991.

  35. 35

    Borg GA . Psychophysical bases of perceived exertion. Med Sci Sports Exerc 1982; 14: 377–381.

  36. 36

    Maughan RJ . A simple, rapid method for determination of glucose, lactate, pyruvate, alanine, 3-hydroxybutyrate and acetoacetate in a single 2 μl blood sample. Clin Chem Acta 1982; 122: 231–240.

  37. 37

    Mc Conway MG, Johnson D, Kelly A, Griffin D, Smith J, Wallace AM . Differences in circulating concentrations of total, free and bound leptin relate to gender and body composition in adult humans. Ann Clin Biochem 2000; 37: 717–723.

  38. 38

    Caro JF, Sinha MK, Kolaczynski JW, Zhang PL, Considine RV . Leptin: the tale of an obesity gene. Diabetes 1996; 45: 1455–1462.

  39. 39

    Banks WA, DiPalma CR, Farrell CL . Impaired transport of leptin across the blood–brain barrier in obesity. Peptides 1999; 20: 1341–1345.

  40. 40

    Banks WA . Enhanced leptin transport across the blood–brain barrier by α1 adrenergic agents. Brain Res 2001; 899: 209–217.

  41. 41

    Cryer PE . Adrenaline: a physiological metabolic regulatory hormone in humans? Int J Obes Relat Metab Disord 1993; 17: 43–46.

  42. 42

    Carulli L, Ferrari S, Bertolini M, Tagliafico E, Del Rio G . Regulation of ob gene expression: evidence for epinephrine-induced suppression in human obesity. J Clin Endocrinol Metab 1999; 84: 3309–3312.

  43. 43

    Couillard C, Mauriege P, Prud'homme D, Nadeau A, Tremblay A, Bouchard C, Despres JP . Plasma leptin response to an epinephrine infusion in lean and obese women. Obes Res 2002; 10: 6–13.

  44. 44

    Flier JS . Clinical review 94: What's in a name? In search of leptin's physiologic role. J Clin Endocrinol Metab 1998; 83: 1407–1413.

  45. 45

    Raben A, Kiens B, Richter EA . Differences in glycaemia, hormonal response and energy expenditure after a meal rich in mono- and disaccharides compared to a meal rich in polysaccharides in physically fit and sedentary subjects. Clin Physiol 1994; 14: 267–280.

  46. 46

    Raben A, Macdonald I, Astrup A . Replacement of dietary fat by sucrose or starch: effects on 14 d ad libitum energy intake, energy expenditure and body weight in formerly obese and never-obese subjects. Int J Obes Relat Metab Disord 1997; 21: 846–859.

  47. 47

    Cowburn G, Hillsdon M, Hankey CR . Obesity management by life-style strategies. Br Med Bull 1997; 53: 389–408.

  48. 48

    Wing RR, Hill JO . Successful weight loss maintenance. Annu Rev Nutr 2001; 21: 323–341.

  49. 49

    Pollock ML . Prescribing exercise for fitness and adherence. In: Dishman RK (ed). Exercise adherence. Human Kinetics Publishers: Champain, 2L; 1988 pp 259–277.

  50. 50

    Andersson I, Rossner S . Meal patterns in obese and normal weight men: the ‘Gustaf’ study. Eur J Clin Nutr 1996; 50: 639–646.

  51. 51

    Mayer J, Thomas DW . Regulation of food intake and obesity. Science 1967; 156: 328–337.

  52. 52

    Hukshorn CJ, Saris WH, Westerterp-Plantenga MS, Farid AR, Smith FJ, Campfield LA . Weekly subcutaneous pegylated recombinant native human leptin (PEG-OB) administration in obese men. J Clin Endocrinol Metab 2000; 85: 4003–4009.

Download references

Acknowledgements

This study was supported in part by a grant from IKY (State Scholarships Foundation, Greece). The authors have no conflicts of interest to declare.

Author information

Correspondence to M E J Lean.

Rights and permissions

Reprints and Permissions

About this article

Keywords

  • appetite regulation
  • leptin
  • eating
  • energy intake
  • physical activity

Further reading