Journal of the American College of Nutrition, Vol. 22, No. 3, 247-251 (2003)
Published by the American College of Nutrition
Postprandial Leptin Response to Carbohydrate and Fat Meals in Obese Women
Monique Romon, MD, PhD,
Pascal Lebel, MSc,
Jean-Charles Fruchart, PhD and
Jean Dallongeville, MD, PhD
Service de Nutrition, Faculté de Médecine (M.R.), Institut Pasteur Lille, Lille Cedex, FRANCE
INSERM U 545 (P.L., J.-C.F.), Institut Pasteur Lille, Lille Cedex, FRANCE
INSERM U 508 (J.D.), Institut Pasteur Lille, Lille Cedex, FRANCE
Address reprint requests to: Monique Romon, MD, PhD, Service de Nutrition, Faculté de Médecine, 59045 Lille Cedex, FRANCE. E-mail: mromon{at}univ-lille2.fr
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ABSTRACT
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Objective: To assess the postprandial leptin responses to a carbohydrate and a fatty meal in obese subjects and its association with postprandial insulin response.
Methods: Eight obese and 11 lean women were given, in a random order, an isocaloric carbohydrate meal (3.43 MJ, 166g of carbohydrates, 38g of proteins) or fat meal (3.35 MJ, 70g of fat, 36g of proteins) or remained fasting. Blood samples were collected hourly during the nine hours after the meal for leptin, insulin, C-peptide and glucose determinations.
Results: In obese subjects, as in lean subjects, postprandial leptin response, calculated as the increment above fasting values, was higher after the carbohydrate meal than after the fatty meal (p < 0.01). However, after the carbohydrate meal, postprandial leptin increment was lower (p < 0.05) in obese subjects than in lean controls. In contrast, there was no difference in postprandial leptin response between lean and obese subjects after the fatty meal. Correlation analyses showed that the area under the postprandial leptin response curve (leptin AUC) was correlated to insulin AUC in lean (r = 0.70, p < 0.01), but not in obese subjects.
Conclusion: These results indicate that postprandial leptin response is lower after a carbohydrate meal in obese women than in lean controls, suggesting an impairment of postprandial leptin regulation in obese women.
Key words: leptin, insulin, obesity, carbohydrate
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INTRODUCTION
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Energy intake is regulated by sequential mechanisms described by Blundell as a satiety cascade [1]. Carbohydrate and fat affect satiety and hunger through distinct mechanisms. Immediately after a meal, lipids act via cholecystokinine and digestive factors [2]. In contrast, insulin has an important role in regulating carbohydrate-induced satiety [3,4]. The long-term regulation of food intake is partly dependent on leptin, which acts as part of a feedback loop regulating the adipose tissue mass. Therefore, leptin levels decrease during fasting [5] and rise after food intake [6–8].
Several studies have reported that the leptin response to dietary interventions depends on macronutrient content [9,10]. Recently, we have demonstrated in lean subjects that postprandial leptin changes are higher after a carbohydrate meal than after a fat meal [11]. In the later study, leptin response was positively correlated to postprandial insulin changes, suggesting that insulin influences the postprandial regulation of leptin levels.
Since postprandial leptin and insulin changes are closely linked, an impairment of insulin metabolism might affect postprandial regulation of leptin levels. Obesity is associated with insulin resistance. Therefore, we hypothesized that postprandial leptin response to a meal is altered in obese subjects. The present study was designed to test this hypothesis. To this end, we assessed the postprandial leptin changes after a carbohydrate meal in lean and obese subjects. Moreover, in order to test the specificity of this effect, postprandial leptin changes were also assessed after a fatty meal.
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METHODS
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Subjects
Eight obese women (35 ± 8 years of age) were recruited from the Clinic of Lille University Hospital through personal contacts. The inclusion criteria were body mass index (BMI) < 30 kg/m2 and stable weight (
weight <2 kg in the previous three months). Eleven healthy women (22 ± 2 years of age) were recruited for the study from the University of Lille II through advertisements and posters. The inclusion criteria were BMI < 25 kg/m2 and stable weight ( weight <2 kg in the previous three months). Both obese women and control subjects had a fasting blood sample for screening of diabetes, hyperlipidemia and impaired thyroid, hepatic or renal function. Exclusion criteria were glucose >5.5 mmol/L, triglycerides >2.8 mmol/L, LDL-cholesterol >4.1 mmol/L, high blood pressure (systolic >140 mm Hg and/or diastolic >90 mm Hg), smoking, drug consumption or chronic use of medications.
Each subject was informed about the nature and purpose of the investigation and was enrolled in this study after giving an informed consent. The hospital ethics committee (CCPRB de Lille, CHR et U de Lille) approved the protocol according to the current regulations in France. During the 24 hours preceding each experimental session, the subjects were reminded to refrain from exercise and alcohol consumption. Body fat content was assessed by two-frequency (5 and 100 KHz) bioimpedance analysis (Analycor 2 Spengler, France).
Experimental Design
The study was performed in the Clinical Investigation Center of Lille University Hospital. The experiment used a repeated-measure design in which each subject served as her own control. There were three subsets of dietary experiments named: "carbohydrate load," "fat load" or fasting. The order of presentation was balanced. There was an interval of at least five days between sessions. The two test-loads were isocaloric and were composed of (1) fat-free cottage cheese (500 g) strawberry jam (90 g) and a dextrin-maltose mixture (90 g) for the "carbohydrate load" or (2) fat cream (200 g; 94.5% saturated, 5.5% polyunsaturated) and a protein mixture of cows milk origin (35 g of Protifar Plus, Nutricia, Rueil Malmaison, France) for the "fat load." During the fasting experiment, the subjects had to remain fasting and were allowed to drink water only.
On the day preceding each test, the subjects were asked to finish their last meal before 20:00. On the test-day, the subjects arrived at the research center at 07:30. They were weighed after voiding their bladder. An indwelling venous cannula was inserted into an antecubital vein before the test-load. At 08:00, a baseline blood sample was taken and the participants were given the test-load and instructed to consume it completely within a maximum time of 20 minutes. Afterwards, blood samples were drawn hourly for nine hours.
Biochemical Measurements
Blood was collected into EDTA tubes. Plasma was separated by centrifugation 3,300 g for 20 minutes at 4° C. Glucose was determined enzymatically (Glucose, Hexokinase Method, Randox Laboratories Ltd., UK). Hormone levels were determined using commercially available immunological assays. Insulin was measured by radioimmunoassay (Bi-Insulin RIA, ERIA, Diagnostics Pasteur, France). C-peptide levels were determined by RIA (RIA-Coat C-Peptide III, Byk Sangtec Diagnostica, Dietzenbach, Germany). Leptin levels were determined in duplicate by radioimmunoassay (Human Leptin RIA Kit, Wak-Chemie, Medical GMBH, Germany). The lower limit of sensitivity of the assay is 0.5 ng/mL. For values between 1.3 and 1.9 ng/mL the intra- and inter-assay variability was 3.7% and 12.6%, respectively.
Statistical Analysis
Student’s t test was used to compare clinical characteristics of lean and obese subjects. One way ANOVA was used to compare baseline biological variables before experimental meals. The postprandial response was measured as follows: Vx-Vfasting, where Vx, and Vfasting are the values of the variable at time x after a meal and during fasting, respectively; x varied between baseline and nine hours. Two-way analysis of variance (ANOVA) was performed to assess the effect of "time" (repeated factor 10 levels: 0 to 9 hours), "weight" (2 levels: lean/obese) or "meal" (repeated factor 3 levels: carbohydrate/fat/fast) and their interactions on postprandial response. Post-hoc analyses were performed with the Scheffe’s test. Pearson correlation analysis was used to test the association between postprandial leptin and insulin responses. To this end, the area under the postprandial response curve (AUC) was assessed by 
, Vx-V0. Differences were considered statistically significant when p was below 5%.
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RESULTS
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The baseline characteristics of lean and obese women are presented in Table 1. Age, weight, body mass index, fat-free mass and fat mass were higher (p < 0.0001) in obese women than in lean control. Table 2 shows plasma leptin levels of lean and obese subjects before each experimental condition. Leptin levels were higher in obese than in lean women (p < 0.0001). There was no statistically significant difference of baseline leptin levels among groups in lean or obese subjects.
Fig. 1 presents the postprandial insulin, C-peptide and glucose levels in lean and obese subjects during the carbohydrate, fatty meal and fasting experiment. After the carbohydrate meal and to a much lesser extent after the fatty meal, both insulin and C-peptide increased markedly in lean and obese subjects. Glucose increased markedly after the carbohydrate meal in obese, but not in lean subjects.
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Fig. 1. Insulin, C-peptide and glucose levels before and after the carbohydrate and the fat meal in lean and obese women.
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Fig. 2 shows the postprandial leptin levels in lean and obese subjects before and after the carbohydrate and the fatty meals, as well as during the fasting experiment. As expected leptin levels were higher at all time point in obese subjects than in lean controls. Two-way ANOVA showed an interaction (p < 0.001) between "meal" (carbohydrate/fat/fast) and "time" (0h, 1h, ..., 9h) in lean and obese subjects. This indicates that leptin levels differ among meals. In lean and obese subjects, leptin increased after the carbohydrate meal, remained stable after the fatty meal and decreased during fasting.
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Fig. 2. Leptin levels before and after the carbohydrate and the fat meal in lean and obese women and during the fasting experiment. Statistical analyses were carried out separately in lean and obese subjects. Two-way ANOVA with "time" (repeated factor 10 levels: 0 to 9 hours) and "meal" (repeated measures: carbohydrate/fat/fast) and their interaction was used for statistical analyses. Statistically significant (p < 0.001) interactions were found between the two factors in both lean and obese subjects.
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Fig. 3 presents the postprandial leptin response in lean and obese subjects after the carbohydrate and the fatty meal. After the carbohydrate meal, two-way ANOVA showed an interaction (p < 0.002) between "weight status" (lean/obese) and "time" (0h, 1h, ..., 9h) for leptin response. This indicates that the leptin response to the carbohydrate meal is lower in obese subjects than in lean controls. In contrast, there was no evidence for any statistically significant difference in leptin response between lean and obese subjects after the fat meal.
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Fig. 3. Postprandial leptin response to the carbohydrate and the fat meal in lean and obese women. Leptin response was calculated as the difference with the corresponding fasting value of the continued fast experiment. Two-way ANOVA with weight status ("Weight status") and postprandial time (repeated measured: "Time") and their interaction ("Interaction") was used for statistical analyses. Post-hoc analyses were used to compare obese and lean subjects at each time point (* = p < 0.05).
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In order to evaluate the possible association between postprandial leptin and insulin responses to the meals, a correlation analysis was performed between postprandial leptin and insulin AUC in lean and obese women (Fig. 4). The leptin response was correlated to insulin response in lean (r = 0.70, p < 0.01), but not in obese subjects (r = 0.19, ns).
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Fig. 4. Correlation between postprandial insulin (x-axis) and leptin (y-axis) AUC to the carbohydrate and fat meal in obese (open circles) and lean (dark triangles) women.
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DISCUSSION
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This study was performed to assess the postprandial leptin response of obese subjects. The results showed that in obese women, like in lean subjects [11], the leptin response to a carbohydrate meal was higher than to a fat meal. However, compared to lean controls, the leptin response of obese women was reduced after the carbohydrate meal, but not after the fatty meal. Furthermore, there was a positive relationship between insulin and leptin AUCs in lean, but not in obese women.
These results are in agreement with previous studies that showed that, after a short fast, refeeding resulted in a doubling of leptin levels in normal weight subjects and an increase of only 10% in obese subjects [12]. Similarly, the leptin response to a regular meal was restored after weight reduction in formerly obese subjects [9], further indicating that obesity is associated with an impairment of postprandial leptin response. The present paper adds to the previous ones the notion that this difference between obese and lean subjects is related to the carbohydrate content of the meal and also that the difference is seen shortly after food intake.
The reasons for these differences are not known. One first explanation is that insulin, whose sensitivity is impaired in obese subjects, does not stimulate leptin secretion properly after the carbohydrate meal [13,14]. This hypothesis is based on the observation of a dissociation between the large postprandial insulin changes and the low postprandial leptin response after the carbohydrate meal. It is supported by evidence showing that experimentally-induced insulin resistance diminishes the stimulatory effect of insulin on leptin secretion [15]. Second, since both obese and lean women received the same meal, the relative caloric load was lower for obese than for lean women. In turn, this may result in a lower stimulation of leptin secretion postprandially [16]. However, if the relative energy load was the only determinant of the lower postprandial leptin response in obese women, then a similarly low response should be measured after the isocaloric fatty meal. Since this was not the case, then the relatively lower caloric load is not the only determinant of the lower postprandial leptin response after the carbohydrate meal in obese subjects. Third, obese women were older than lean control. However, the age-difference was relatively small, and both lean and obese women were young. Moreover, a previous study [17] has shown that leptin levels are not different between pre- and post-menopausal women which argues against a major effect of age. Finally, the lower postprandial leptin levels after the carbohydrate meal could theoretically be due to an increased postprandial leptin clearance in obese subjects.
Short-term studies have shown that low-fat high-carbohydrate diets are less effective in promoting weight loss than energy restricted diets in obese [18–20]. In contrast, the results of longer dietary intervention showed more favorable results with high-carbohydrate diets [21–24]. The present study exploring short-term regulation gives some clues to these observations. Although carbohydrate-induced leptin response is decreased in obese subjects, it is larger than after a fatty meal. Therefore, in the long term, postprandial leptin response might be better stimulated with a high-carbohydrate diet than with other diets [18].
In conclusion, the present study indicates that postprandial leptin response to a carbohydrate load is lower in obese than in lean subjects. These results suggest that the physiological regulation of plasma leptin in response to a carbohydrate meal is impaired in obese subjects.
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ACKNOWLEDGMENTS
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The authors would like to thank the staff of the Centre d’Investigation Clinique du CHRU de Lille for their excellent clinical intervention. The help of Mrs. Foster in editorial revision of the manuscript was greatly appreciated.
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FOOTNOTES
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This study was supported by grants from INSERM (#931501) and the French Ministry of Health and National Solidarity.
Received July 29, 2002.
Accepted December 11, 2002.
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ABSTRACT
INTRODUCTION
