Anorexigenic Postprandial Responses of PYY and GLP1 to Slow Ice Cream

European Journal of Endocrinology (2013) 168 429–436 ISSN 0804-4643

CLINICAL STUDY Anorexigenic postprandial responses of PYY and GLP1 to slow ice cream consumption: preservation in obese adolescents, but not in obese adults A E Rigamonti1, F Agosti2, E Compri2, M Giunta1,2, N Marazzi2, E E Muller1, S G Cella1 and A Sartorio2 1Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, Universita` degli Studi di Milano, Via Vanvitelli 32, 20129 Milan, Italy and 2Laboratorio Sperimentale di Ricerche Auxo-Endocrinologiche, Istituto Auxologico Italiano, IRCCS, Milan, Verbania, Italy (Correspondence should be addressed to A E Rigamonti; Email: [email protected])

Abstract Objective: Eating slowly increases the postprandial responses of some anorexigenic gut hormones in healthy lean subjects. As the rate of food intake is positively associated with obesity, the aim of the study was to determine whether eating the same meal at different rates evokes different postprandial anorexigenic responses in obese adolescent and adult subjects. Design and methods: Eighteen obese adolescents and adults were enrolled. A test meal was consumed on two different sessions by each subject, meal duration taking either 5 min (fast feeding) or 30 min (slow feeding). Circulating levels of glucagon-like peptide 1 (GLP1), peptide YY (PYY), glucose, insulin, and triglycerides were measured over 210 min. Visual analog scales were used to evaluate the subjective feelings of hunger and satiety. Results: Fast feeding did not stimulate GLP1 release in obese adolescent and adults, whereas slow feeding increased circulating levels of GLP1 only in obese adolescents. Plasma PYY concentrations increased both in obese adolescents and in adults, irrespective of the eating rate, but slow feeding was more effective in stimulating PYY release in obese adolescents than in adults. Simultaneously, slow feeding evoked a higher satiety only in obese adolescents compared with fast feeding but not in obese adults. In obese adolescents, slow feeding decreased hunger (only at 210 min). Irrespective of the eating rate, postprandial responses of insulin and triglycerides were higher in obese adults than in obese adolescents. Conclusion: Slow feeding leads to higher concentrations of anorexigenic gut peptides and favors satiety in obese adolescents, but this physiological control of food intake is lost in obese adults.

European Journal of Endocrinology 168 429–436

Introduction In accordance, in healthy lean adults, eating at a physiologically moderate pace leads to a more pro- In the USA and Europe, rates of eating and food nounced anorexigenic gut peptide response than eating sizes (fast feeding) have considerably increased in the at a very fast rate. This is reﬂected in peptide YY (PYY) past decades (1, 2). In this context, recent studies have and glucagon-like peptide 1 (GLP1) responses (7), shown that eating large portions in a very short time which, acting on the hypothalamus and brain stem, enhances food intake and is thereby a risk factor for inhibit food intake and stimulate satiety (8). obesity (3, 4). Based on the foregoing arguments, sociopolitical and The lifestyle of the modern civilization facilitates educational interventions directed at limiting eating diffusion of fast feeding and, consequently, high energy rate and portion size might help lean consumers to intake. A high eating rate, combined with distraction of reduce their food intake (2, 9). This becomes even more attention from eating, is believed to undermine the important for obese patients, who reportedly eat faster capacity of the body to regulate its energy intake at than lean individuals (10). Interestingly, in obese healthy levels because these factors impair the congruent patients, eating rate has a positive correlation with association between sensory signals and metabolic adiposity (11), regardless of adjustment for nutrient consequences. A number of studies have shown that intake (11) or subject age (obese children, adolescents, foods eaten quickly lead to high food intake and low and adults) (12). satiating effects because this type of feeding exposes the To the best of our knowledge, postprandial concen- human body to insufﬁcient sensory cues for satiation (5, 6). trations of anorexigenic peptides have not been assessed

q 2013 European Society of Endocrinology DOI: 10.1530/EJE-12-0867 Online version via www.eje-online.org

Downloaded from Bioscientifica.com at 10/02/2021 07:37:51AM via free access 430 A E Rigamonti and others EUROPEAN JOURNAL OF ENDOCRINOLOGY (2013) 168 in blood of obese patients in the context of different rates in a random order. After a 12-h fast, subjects began of eating behavior. As the obese state tends to worsen in each of the two tests at the same period, between 0800 an age-dependent manner (13), an intriguing possi- and 0830 h. The subjects were instructed to adhere to bility is that eating more slowly will induce more satiety the diet and physical activity patterns of the day and higher concentrations of anorexigenic peptides only preceding each test and to abstain from strenuous in an early phase of obesity (e.g. obese adolescents), a physical exertion, caffeine, and smoking during the physiological control of food intake that would be lost 12-h fast. Twenty-four-hour diet and activity recalls after many years of the obese state and the related were completed during each test to ensure compliance insulin resistance (e.g. obese adults). Hence, this study with these instructions. To maintain a stable daily examined possible differences in the postprandial caloric intake of the in-hospital patients, the amount of responses of GLP1, PYY, glucose, insulin, and triglycer- foods administered at lunch and dinner of the ides when identical meals were consumed in two experimental days was proportionally reduced to separate sessions of different duration (fast feeding vs account for the calories of the test meal. slow feeding) by two groups of obese patients, i.e. During each of the two tests, an intravenous cannula adolescents and adults. for blood sampling was inserted into a superficial forearm vein and kept patent by isotonic saline water infusion. All subjects consumed the same test meal of 10 kcal/kg ice cream for a maximum of 510 g (85 g, Materials and methods 59% of kcal fat, 33% carbohydrates, and 8% protein; lipid composition for 100 g of the product: monounsa- Subjects turated fatty acids, 3.49 g; polyunsaturated fatty acids, Obese adolescents (age, 16.7G0.4 years; F/M, 6/3; 0.45 g; saturated fatty acids, 7.48 g; and cholesterol, BMI, 37.2G2.4 kg/m2) and adults (age, 30.1G3.2 91 mg) at different rates. In one session (fast feeding), years; F/M, 7/2; BMI, 44.1G1.9 kg/m2) were recruited the entire meal was consumed within 5 min, whereas in from the Istituto Auxologico Italiano, IRCCS, Verbania, the other (slow feeding) it was divided into six equal Italy, to which they were admitted for a multi- portions, which were given to the subject every 5 min disciplinary weight reduction intervention. All adults and consumed within 30 min. Subjects were instructed were obese since pubertal age. Exclusion criteria to finish each portion in !1 min to maintain a uniform included previous diagnosis of any disease affecting rate of meal ingestion. Qualitative and quantitative the endocrine system and metabolism (apart from characteristics of the test meal were chosen to elicit obesity), chronic use of medications (including oral robust responses in PYY and GLP1 in lean subjects (our contraceptives) affecting metabolism and/or appetite, personal experience and reference (7)). R5.0 kg weight change during the 3 months preceding Blood samples for the measurement of glucose, study participation, pregnancy, allergies to or stated insulin, triglycerides, PYY, and GLP1 were drawn before dislike of the components of the test meal (see below), the meal and at 30-min intervals after the beginning of and clinically diagnosed eating disorder or a score of meal consumption until the end of the session 210 min R20 on the Eating Attitudes Test (14). All females were later. Visual analog scales (VASs) for assessment of the eumenorrheic, apart from a single adult woman who subjective feelings of hunger and satiety were completed suffered from hypooligomenorrhea, in whom a diag- before the meal and at 30-min intervals after meal nosis of polycystic ovary syndrome was ruled out. The termination until the end of the study session. two experimental groups (obese adolescents and adults) were socioeconomically homogenous when evaluated by a specific questionnaire (15). The study was Biochemical assays approved by the Local Ethics Committee. All subjects Total plasma PYY level, including both PYY1–36 and participated in this study after providing their free and PYY3–36, was measured by a commercially available informed consent. In cases when the subject was !18 RIA for PYY (Millipore, Saint Charles, MO, USA). The years old, consent was provided by his/her parents. sensitivity of the method was 10 pg/ml; intra- and interassay coefficients of variation (CV) were 2.9 and Study design 7.1% respectively. Total plasma GLP1 level, including GLP17–36 amide, Anthropometric characteristics were evaluated during GLP17–37, GLP19–36 amide, GLP19–37, GLP11–36 amide, the screening period. BMI was calculated from and GLP11–37, was measured, after an extraction measured height and weight. Fat-free mass (FFM) and procedure, by RIA (Millipore). A DPP-4 inhibitor was fat mass (FM) were evaluated by bioelectrical impedance added to tubes to prevent the breakdown of GLP1. The analysis (Human-IM Scan, DS-Medigroup, Milan, Italy). sensitivity of the method was 3 pmol/l; intra- and The experimental period comprised two separate tests interassay CV were 2.9 and 7.1% respectively. occurring on nonconsecutive days over at least 2 weeks. Serum insulin concentration was determined by The tests (fast feeding or slow feeding) were performed chemiluminescent immunometric assay using a

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Downloaded from Bioscientifica.com at 10/02/2021 07:37:51AM via free access EUROPEAN JOURNAL OF ENDOCRINOLOGY (2013) 168 GLP-1, PYY, and satiety to slow feeding in obesity 431 commercial kit (Immulite 2000, DPC, Los Angeles, CA, Table 1 Baseline demographic, clinical, hormonal, and metabolic USA). The sensitivity of the method was 2 mIU/ml; intra- characteristics of the patients enrolled in the study. and interassay CV were 22–38% and 14–23% respectively. Adolescent Adult Serum glucose level was measured by the glucose Age (years) 16.7G0.4 30.1G3.2* oxidase enzymatic method (Roche Diagnostics). Serum tri- Gender (F/M) 6/3 7/2 glycerides levels were quantified by a colorimetric enzy- BMI (kg/m2) 37.2G2.4 44.1G1.9* G G matic method (Wako Chemical GmbH, Neuss, Germany). FFM (%) 56.4 2.2 48.3 2.3* FM (%) 43.6G2.2 51.7G2.3* GLP1 (pmol/l) 13.5G2.4 18.0G5.6 PYY (pg/ml) 85.5G4.4 90.3G7.1 Statistical analysis Glucose (mg/dl) 81.6G1.5 88.2G1.6* G Triglycerides (mg/dl) 65.6G4.2 101.9G14.2* Results are reported as mean S.E.M. Homeostasis model Insulin (mIU/ml) 8.1G1.7 14.0G1.9* of assessment of insulin resistance (HOMA-IR) was HOMA-IR 1.6G0.4 3.1G0.5* calculated by the formula: (insulin (mIU/ml)!glucose (mg/dl))/405. The responses in glucose, insulin, *P!0.05 vs obese adolescents. FFM, fat-free mass; FM, fat mass; GLP1, glucagon-like peptide 1; PYY, peptide YY. triglycerides, PYY, and GLP1 and VASs for hunger and satiety were evaluated as absolute values and also as 210 min postprandially (P!0.05); the same increases area under the curve (AUC) of postprandial measure- in plasma GLP1 levels were recorded at all time points in ments using the trapezoid rule for each session (fast fast and slowly fed obese adults (P!0.05) (Fig. 1). feeding and slow feeding). When obese adolescents were slowly fed, plasma PYY Despite a female prevalence in the recruited popu- levels were significantly higher than values stimulated lation, there were no statistical differences in any of the by fast feeding at 90, 120, and 180 min; a statistically investigated parameters in each group between females significant difference was present in obese adults only at and males. Thus, data of all subjects of the same group ! were pooled. 120 min (P 0.05; Fig. 1). In contrast to obese adults, All parameters (glucose, insulin, triglycerides, PYY, in obese adolescents, the AUC for GLP1 response over GLP1, and VASs for hunger and satiety) were compared 210 min was significantly higher after slow feeding ! within each group (obese adolescents or adults) and than fast feeding (P 0.05); in addition, slow feeding among the two eating rates (fast feeding and slow induced a significantly higher GLP1 response in obese feeding) using a two-way ANOVA with repeated adolescents than in obese adults (P!0.05) (Fig. 2). measures followed by the post hoc Bonferroni’s test. There were no differences in the AUCs for postprandial One-way ANOVA was used to compare the AUCs of the PYY responses over 210 min in obese adolescents and four groups (obese adolescents and adults!fast feeding adults, when fast or slowly fed (inter- and intra-groups and slow feeding). The other demographic, clinical, comparisons; Fig. 2). metabolic, and hormonal characteristics of the study Irrespective of the eating rate, there were significant subjects were analyzed by Student’s t-test for unpaired decreases and increases in hunger and satiety VAS data. Correlations were evaluated by calculation of Pearson’s product-moment coefficients (for all data). A 100 Adolescents 100 Adults FAST-Feeding FAST-Feeding stepwise multiple regression was used to test the 80 SLOW-Feeding 80 SLOW-Feeding influence of age, weight, BMI, and HOMA-IR on 60 60 postprandial changes in circulating PYY and GLP1 40 40 GLP1 (pmol/l) GLP1 (pmol/l) after slow and fast feeding. A P value of 0.05 was chosen 20 20 as statistically significant. 0 0 03060 90 120150180210 0 30 60 90 120150180210 Time (min) Time (min)

200 200 Results 150 150

Baseline demographic, clinical, hormonal, and meta- 100 100

bolic characteristics of the study subjects are reported in PYY (pg/ml) PYY (pg/ml) 50 FAST-Feeding 50 FAST-Feeding Table 1. Only slow feeding significantly increased SLOW-Feeding SLOW-Feeding plasma concentrations of GLP1 in obese adolescents 0 0 0 30 60 90 120 150 180 210 0 30 60 90 120 150 180 210 (P!0.05), whereas neither fast nor slow feeding Time (min) Time (min) significantly changed plasma levels of GLP1 in obese adults (Fig. 1). Irrespective of the eating rate, food intake Figure 1 Plasma concentration of GLP1 and PYY after a 10 kcal/kg significantly increased circulating levels of PYY in both meal eaten in 5 min (fast feeding) or 30 min (slow feeding) by obese groups (P!0.05; Fig. 1). Interestingly, plasma GLP1 adolescents or adults. Both meals were administered at 0 min. Values are expressed as meanGS.E.M.*P!0.05 vs the corre- ! concentrations were higher after slow feeding than fast sponding time point of the fast feeding; P!0.05 vs the feeding in obese adolescents at 90, 120, 150, 180, and corresponding baseline value (T0).

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15000 * 20000 Adolescents glucose were positively correlated with those of insulin * Adults (rZ0.48, P!0.05); furthermore, there were positive Adolescents 15000 10000 Adults correlations between BMI and FM (rZ0.64, P!0.05) 10000 or baseline serum levels of triglycerides (rZ0.43, 5000 5000 P!0.05). HOMA-IR was positively correlated with PYY AUC (pg/ml×min) PYY AUC GLP1 AUC (pmol/l×min) GLP1 AUC 0 0 BMI (rZ0.68, P!0.01), FM (rZ0.65, P!0.01), SLOW-FEEDING FAST-FEEDING SLOW-FEEDING FAST-FEEDING glucose (rZ0.56, P!0.01), and insulin (rZ0.99, 15000 25000 Adolescents Adolescents P!0.01). Despite the negative correlation between Adults 20000 Adults m×min) m×min) µ 10000 µ plasma levels of PYY (but not GLP1) and FM 15000 (rZK0.41, P!0.05), there were no correlations 10000 5000 between AUCs of GLP1 or PYY to slow feeding and 5000 fast feeding and BMI or FM. Interestingly, baseline Satiety VAS AUC ( AUC VAS Satiety Hunger VAS AUC ( AUC VAS Hunger 0 0 SLOW-FEEDING FAST-FEEDING SLOW-FOOD FAST-FEEDING serum levels of glucose, insulin, and HOMA-IR were negatively correlated with AUCs of GLP1 (rZK0.66, Figure 2 Values of area under the curve (AUC) over 210 min for rZK0.49, and rZK0.54 respectively, P!0.05) or plasma concentrations of GLP1 and PYY and VAS ratings of hunger PYY (rZK0.40, rZK0.42, and rZK0.47 respect- and satiety in obese adolescents and adults administered with a 10 kcal/kg meal at different rate (5 min for fast feeding and 30 min ively) to slow feeding, but not to fast feeding; AUC of for slow feeding). Values are expressed as meanGS.E.M.*P!0.05. PYY (but not GLP1) to slow feeding was positively correlated with that to fast feeding (rZ0.61, P!0.05). ratings respectively after food intake in both groups (P!0.05; Fig. 3). The hunger VAS rating was significantly lower at 210 min in slowly fed obese Discussion adolescents, when compared with that recorded after fast feeding (P!0.05); there was no difference in obese The anorexigenic peptides GLP1 and PYY are released adults (Fig. 3). The satiety VAS rating was higher in in response to nutrient ingestion from endocrine L cells, obese adolescents after slow feeding than fast feeding most densely located in the distal ileum (16, 17, 18, 19, from 120 min to the end of the study (210 min; 20, 21). Importantly, administration of GLP1 or PYY P!0.05); there were the same increases in the satiety reduced energy intake in both lean and overweight VAS rating for all time points in fast and slowly fed obese subjects (22). The hypothalamus and the brainstem adults (Fig. 3). There were no significant differences in are thought to be the most relevant areas of satiating AUCs for hunger and satiety VAS ratings over 210 min and hypophagic effects of peripheral GLP1 and PYY between the two groups at different eating pace (intra- (23, 24). and inter-group comparisons; Fig. 2). In this study, eating at a physiologically slow pace Irrespective of the eating rate, there were significant (slow feeding) led to a more pronounced anorexigenic increases in serum levels of glucose and insulin after peptide response than eating fast (fast feeding) in obese food intake in both groups, whereas levels of triglycerides significantly increased only in obese adolescents 100 Adolescents 100 Adults

! FAST-FEEDING * FAST-FEEDING m) (P 0.05; Fig. 4). There were the same increases in m) µ µ SLOW-FEEDING SLOW-FEEDING serum concentrations of glucose, insulin, and triglycer- 50 50 ides at all time points in both obese adolescents and VAS hunger ( VAS adults, fast and slowly fed (Fig. 4). There were hunger ( VAS signiﬁcant differences in AUCs for serum levels of 0 0 insulin and triglycerides over 210 min between the 0 30 60 90 120 150 180 210 0 30 60 90 120 150 180 210 two groups when fast or slowly fed (P!0.05; Fig. 5). Time (min) Time (min) To assess whether postprandial changes in circulat- 100 100 m) ing PYY and GLP1 after slow and fast feeding, expressed m) µ µ as differences in maximum percent increases from 50 50 preprandial values, were related to age, weight, BMI,

VAS satiety ( VAS FAST-FEEDING FAST-FEEDING VAS satiety ( VAS and HOMA-IR, a stepwise multiple regression with PYY SLOW-FEEDING SLOW-FEEDING or GLP1 as dependent variable and age, weight, BMI, 0 0 0 30 60 90 120 150 180 210 0 30 60 90 120 150 180 210 and HOMA-IR as independent variables was run. This Time (min) Time (min) analysis showed that across all the subjects, no signiﬁcant effect emerged between these variables Figure 3 Changes of VAS ratings of hunger and satiety after a when the two subject groups (adolescents and adults) 10 kcal/kg meal eaten in 5 min (fast feeding) or 30 min (slow were assessed separately or together. feeding) by obese adolescents or adults. Both meals were administered at 0 min. Values are expressed as meanGS.E.M. As expected, BMI and FM were positively correlated *P!0.05 vs the corresponding time point of fast feeding (satiety) or with baseline serum levels of insulin (rZ0.70, rZ0.67 slow feeding (hunger); !P!0.05 vs the corresponding baseline respectively, P!0.05); baseline serum levels of value (T0).

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FAST-FEEDING on the contrary, would be maintained in obese SLOW-FEEDING adolescents as in lean adults (7). Analogously, changes 150 Adolescents 150 Adults × in the concentrations of the adipokines, e.g. leptin and

× × adiponectin, occurred with worsening and persistence 100 100 × × × of obesity over time (13). Further studies are needed to

50 50 demonstrate the involvement of these adipokines Glucose (mg/dl) Glucose (mg/dl) (or other factors?) in the loss of increased anorexigenic

0 0 peptide production after a slow meal in obese adults. 0 30 60 90 120 150 180 210 0 30 60 90 120 150 180 210 In this study, slow feeding evoked a higher satiety Time (min) Time (min) in obese adolescents but not in obese adults. In addition, 150 150 ×× in obese adolescents, there was a signiﬁcant decrease in × × hunger after slow feeding (at 210 min). These ﬁndings are 100 × 100 × × × × × fully congruent with the potent anorexigenic responses of × 50 × × 50 GLP1 and PYY to slow feeding in obese adolescents. Insulin (µIU/ml) Insulin (µIU/ml) × In our opinion, though VAS is the best tool to evaluate 0 0 proneness to feeding or satiety, it remains a subjective 0 30 60 90 120 150 180 210 0 30 60 90 120 150 180 210 expression of a person’s perceptions. Therefore, VAS may Time (min) Time (min)

200 200 not have been sensitive enough to discern subtle differences in obese adults administered with food at 150 150 different paces (28). Nonetheless, irrespective of the × × × 100 100 × eating pace, food intake markedly reduced or increased × × hunger and satiety respectively,also in obese adults, when 50 50 Triglycerides (mg/dl) Triglycerides (mg/dl) Triglycerides the two parameters were compared with the baseline 0 0 0 30 60 90 120 150 180 210 0 30 60 90 120 150 180 210 conditions. Thus, the unchanged hunger and satiety in

Time (min) Time (min) this group after fast and slow feeding could be interpreted as the inability of slow feeding to enhance plasma rise of Figure 4 Plasma concentration of glucose, insulin, and triglycerides GLP1 and PYY and to stimulate a valid anorexigenic after a 10 kcal/kg meal eaten in 5 min (fast feeding) or 30 min (slow response at central level. Noteworthily, despite significant feeding) by obese adolescents or adults. Both meals were administered at 0 min. Values are expressed as meanGS.E.M. differences in postprandial GLP1 and PYY levels or !P!0.05 vs the corresponding baseline value (T0). satiety and hunger ratings between obese adolescents and adults, there was no significant difference in PYY adolescents, whereas obese adults showed only negli- response or hunger and satiety perception when assessed gible differences. In particular, while fast feeding did not by AUC. This might be due to the long-lasting evaluation stimulate GLP1 release in either group, only in obese of the postprandial responses (210 min), which was adolescents was slow feeding capable of increasing entirely used for the calculation of AUC values, and to the intersubject variability, which impeded to obtain a circulating levels of GLP1. Furthermore, compared with statistically significant difference. the baseline condition, plasma PYY concentrations Given that PYY is released within 15 min of food were increased by food intake irrespective of the eating intake, this must occur before the ingested nutrients pace. Finally, slow feeding was more effective in reach the distal small intestine and colon (where the stimulating PYY release in obese adolescents than in greatest concentrations of PYY are present). Therefore, obese adults. initial postprandial release of PYY is likely to be under Obesity has been associated with attenuation of the neural control. Further release of PYY is observed when postprandial responses of GLP1 and PYY (22, 25).In the nutrients arrive to the distal gut and the release addition, a negative correlation has been reported is particularly stimulated by a high-fat diet (21, 22). between circulating levels of these anorexigenic peptides Also GLP1 shows a biphasic response after a meal, the and adiposity, evaluated as BMI and FM (26, 27). In this first peak occurring before nutrients enter the distal gut study, despite a significant difference in BMI between the and is augmented by a high-carbohydrate meal (29). two groups, there was no correlation between post- In this study, the enhancement of GLP1 and PYY prandial responses in GLP1 and PYY and BMI or FM. responses after slow feeding in obese adolescents Furthermore, a stepwise multiple regression showed no appeared at 90 min. This finding seems to detract the influence of BMI on postprandial changes in circulating contribution of neural control to the anorexigenic PYY and GLP1 after slow and fast feeding. Although the effects of slow feeding. The hypothesis that fast feeding small sample size may have impeded to unveil any provides brief periods of sensory exposure and insuffi- statistically significant difference, these findings would cient cues for satiation has to be reevaluated taking into imply a causative role to the long-lasting obesity state in account the findings of this study (5, 6). adults (about 15–20 years), disrupting the physiological Multiple studies have shown the association of control of GLP1 and PYY postprandial elevation which, pediatric and adolescent obesity with obesity in adults.

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25000 Adolescents Adults components of the metabolic syndrome (34, 35). These considerations are supported by the metabolic ﬁndings

20000 of our study, and particularly the postprandial insulin and triglycerides responses were higher in obese adults

15000 than in obese adolescents. As time of insulin resistance is not equal to time of obesity exposure, further studies are necessary to demonstrate the involvement of 10000 age-related worsening of insulin resistance in the ineffectiveness of slow feeding to increase the post- Glycemia AUC (mg/dl×min) Glycemia AUC 5000 prandial anorexigenic response in obese adults. Anyway, it is noteworthy recalling that, in this study, baseline 0 serum levels of glucose and insulin, as well as HOMA-IR, SLOW-FEEDING FAST-FEEDING were negatively correlated with postprandial rises of

Adolescents Adults GLP1 and PYY to slow feeding, but not to fast feeding. 20000 * * Furthermore, a bidirectional interaction has been reported to exist between insulin and the anorexigenic gut peptides such as GLP1 and PYY (36, 37). 15000 Some limitations of this study have to be mentioned. First, there was no control group formed by lean adolescents and adults, who would have allowed a 10000 better dissection of the effects of body weight and age on the studied parameters. So, the slight difference in BMI

5000 between both groups might have been a potential Glycemia AUC (mg/dl×min) Glycemia AUC confounder in the interpretation of the results of this study. Secondly, though there were no statistically 0 signiﬁcant differences in all investigated parameters SLOW-FEEDING FAST-FEEDING between females and males in each group, there was a female preponderance in the recruited population. Adolescents Adults Therefore, the results of this study should be conﬁrmed * * 30000 in a larger number of sex-matched subjects. Thirdly, the composition of the test meal did not correspond to the standard recommended diet; thus, a different test meal might have provided different results. None- 20000 theless, we chose ice cream because it is a qualitatively homogenous and highly palatable meal that may be easily administered in an experimental context and quickly consumed (only 5 min). 10000 In conclusion, this study demonstrates that eating

Triglycerides AUC (mg/dl×min) AUC Triglycerides the same meal over 30 min instead of 5 min leads to higher concentrations of anorexigenic gut peptides and 0 favors satiety in obese adolescents, whereas this SLOW-FEEDING FAST-FEEDING physiological control of food intake is disrupted in Figure 5 Values of AUC over 210 min for serum levels of glucose, obese adults. Therefore, slow feeding might become a insulin, and triglycerides in obese adolescents and adults adminis- dietary behavior to be inserted in any educational tered with a 10 kcal/kg meal at different rate (5 min for fast feeding program for pediatric obesity (38). Before extending the or 30 min for slow feeding). Values are expressed as meanGS.E.M. results to clinical practice, because of the inevitability ! *P 0.05. of the artificial environment of any clinical study, the qualitative composition of the administered meal, and Overweight children/adolescents are more prone to the female predominance in the study population, long- becoming overweight adults, especially at higher BMIs term clinical studies in obese children/adolescents (30). Almost half of overweight adults have been (possibly in a home or school setting) are mandatory overweight adolescents (31). Obesity during adolescence to demonstrate the efficacy of this (absolutely inexpen- is associated with many adverse health consequences sive and safe) preventive intervention. (32), and dietary habits, physical inactivity, and rates and degree of obesity become worse with the transition from adolescence into adulthood (33). A rise in insulin Declaration of interest resistance has also been reported with the persistence of The authors declare that there is no conflict of interest that could be the obese state, as well as with the worsening of various perceived as prejudicing the impartiality of the research reported.

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Funding 13 Biro FM & Wien M. Childhood obesity and adult morbidities. American Journal of Clinical Nutrition 2010 91 1499S–1505S. The study was supported by Progetti di Ricerca Corrente, Istituto (doi:10.3945/ajcn.2010.28701B) Auxologico Italiano, IRCCS, Milan, Italy. 14 Garner DM, Olmsted MP, Bohr Y & Garfinkel PE. The eating attitudes test: psychometric features and clinical correlates. Psychological Medicine 1982 12 871–878. (doi:10.1017/ Author contribution statement S0033291700049163) A E Rigamonti designed the study.A Sartorio, E Compri, and N Marazzi 15 Robert Koch Institut. Bundes-Gesundheits Survey 1998– enrolled the subjects and performed the experiments. F Agosti Questionnaire. In Gesundheitswesen, issue 61, eds Robert Koch elaborated the database and, together with M Giunta, performed the Institut. New York: Georg Thieme Verlag Stuttgart, 1999. analysis of all the parameters. A E Rigamonti analyzed the data and, 16 Adrian TE, Ferri GL, Bacarese-Hamilton AJ, Fuessl HS, Polak JM & together with A Sartorio, wrote the manuscript. E E Muller Bloom SR. Human distribution and release of a putative new gut contributed to data interpretation and discussion writing. All authors hormone, peptide YY. Gastroenterology 1985 89 1070–1077. contributed to the manuscript revision. 17 Ghatei MA, Uttenthal LO, Bryant MG, Christofides ND, Moody AJ & Bloom SR. Molecular forms of glucagon-like immunoreactivity in porcine intestine and pancreas. Endocrinology 1983 112 Acknowledgements 917–923. (doi:10.1210/endo-112-3-917) 18 Orskov C, Rabenhøj L, Wettergren A, Kofod H & Holst JJ. Tissue The authors wish to thank Dr Alessandra De Col, the dieticians, and and plasma concentrations of amidated and glycine-extended the nursing staff at the Division of Auxology (adolescents) and glucagon-like peptide I in humans. Diabetes 1994 43 535–539. 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