Obese Subjects

Glucagon-Like Peptide-1,Peptide YY,Hunger,and Satiety after Gastric Bypass Surgery in Morbidly Obese Subjects

Rosa Mor?′nigo,Violeta Moize ′,Melina Musri,Antonio https://www.360docs.net/doc/859743249.html,cy,Salvador Navarro,Jose ′Lu?′s Mar?′n,Salvadora Delgado,Roser Casamitjana,and Josep Vidal

Obesity Unit (R.M.,V.M.,A.M.L.,S.D.,J.V.)and Departments of Biological Diagnostics (M.M.,J.L.M.,R.C.)and Gastroenterology (S.N.),Hospital Cl?′nic Universitari,08036Barcelona,Spain

Context:The mechanisms underlying weight loss after Roux-en-Y gastric bypass (RYGBP)are not well understood.

Objective:The objective of the study was to assess the changes in active glucagon-like peptide 1(GLP-1)and total peptide YY (PYY)after RYGBP and examine their relationship with changes in hunger and satiety.

Design:This was a prospective study on the changes in active GLP-1,PYY,hunger,and satiety in response to a standardized test meal in nine normal-glucose-tolerant obese subjects [body mass index (BMI)47.4?6.1kg/m 2]before and 6wk after RYGBP.

Results:Before surgery,meal ingestion failed to stimulate GLP-1and PYY secretion.Six weeks after surgery,despite subjects still being markedly obese (BMI 43.6?7.8kg/m 2),the area under the curve 0–120?of GLP-1and of PYY in response to the standardized test

meal were significantly elevated (P ?0.05and P ?0.01,respectively).These hormonal responses were significantly larger (P ?0.01)than those observed in a group matched for the BMI attained 6wk after surgery.The 2.9?1.2-and 1.6?1.9-fold increase,respectively,in the area under the curve 0–120?of GLP-1and PYY were accompanied by a significant decrease in fasting (P ?0.05)and postprandial hunger (P ?0.05)and a significant increase in satiety (P ?0.05)after meal intake.Nevertheless,a significant correlation between changes in the hormonal and eating behavior parameters was not found.

Conclusion:Our data show that RYGBP is associated with an im-provement in the active GLP-1and total PYY response to a liquid-meal intake.Moreover,we provide circumstantial evidence for a po-tential role of these gastrointestinal hormones on the decreased appetite after RYGBP.(J Clin Endocrinol Metab 91:1735–1740,2006)

B

ARIATRIC SURGERY SUCH as the Roux-en-Y gastric bypass (RYGBP)results in major and sustained weight loss in patients with severe obesity (1).However,the mech-anisms by which RYGBP induces weight loss are not well understood (2,3).RYGBP combines gastric restriction and significant bypass of the stomach and proximal intestine (1,4).Gastric volume restriction is an important determinant of increased satiety after laparoscopic adjustable gastric band-ing (5),suggesting that the creation of a small gastric pouch such as in the RYGBP plays an important role in the early satiation and sustained depressed appetite that occurs after this type of bariatric surgery (6,7).Nonetheless,because malabsorption does not appear to play a major role after short-limb RYGBP (4),it has been hypothesized that a dis-ruption in other factors in the network of signals involved in energy balance (8)accounts for plain gastric restrictive op-erations being less effective than gastric bypass surgery (1,9).Gut-derived hormones have important sensing and sig-naling roles in the regulation of energy homeostasis (10).

Thus,it has been hypothesized that a putative critical factor to the efficacy of RYGBP is change in the gut-derived hor-mones known to influence appetite (2,3).In recent years,numerous reports have evaluated the gastrointestinal endo-crine changes associated with RYGBP.Of note,Cummings et al.(11)first reported that despite massive weight loss,plasma levels of the stomach-derived orexigenic hormone ghrelin were paradoxically suppressed in patients who had under-gone RYGBP,suggesting that this hormone was critical in the suppressed appetite and weight reduction after gastric by-pass surgery.Nevertheless,subsequent studies have shown mixed results,making it hard to sustain this hypothesis (12).In sharp contrast with ghrelin,other gut hormones such as glucagon-like peptide 1(GLP-1)and peptide YY (PYY)act as appetite suppressant agents (10).GLP-1and PYY are re-leased in response to nutrient ingestion from endocrine L cells,most densely located in the distal ileum.GLP-1is the result of posttranslational proteolytic processing of the pre-proglucagon gene in the gut.Under physiological conditions,GLP-1acts primarily to augment insulin secretion after oral glucose or meal ingestion and also decelerates gastric emp-tying and intestinal transit time (13).PYY has also been implicated as a major component of the ileal brake (14).In addition,GLP-1or PYY infusion reduces energy intake in both lean and overweight subjects (15–17).Notably,entero-glucagon levels (used in the past as a marker of intestinal peptides derived from proglucagon)are increased after

First Published Online February 14,2006

Abbreviations:AUC,Area under the curve;BMI,body mass index;GE,gastric emptying;GLP,glucagon-like peptide;OCTT,orocecal tran-sit time;PYY,peptide YY;RYGBP,Roux-en-Y gastric bypass;VAS,visual analog scale;VBG,vertical banded gastroplasty.

JCEM is published monthly by The Endocrine Society (https://www.360docs.net/doc/859743249.html,),the foremost professional society serving the en-docrine community.

0021-972X/06/$15.00/0The Journal of Clinical Endocrinology &Metabolism 91(5):1735–1740

Printed in U.S.A.

Copyright ?2006by The Endocrine Society

doi:10.1210/jc.2005-0904

1735

RYGB(18).Moreover,GLP-1and PYY plasma concentration in response to nutrient intake was enlarged in recent cross-sectional studies in RYGB-operated subjects(19,20).Finally, both GLP-1and PYY levels increase after surgeries that ex-pedite nutrient delivery to the hindgut and are associated with weight loss such as in jeunoileal bypass surgery in humans(21)and ileal transposition in a rodent model(22). Therefore,it could be hypothesized that an accelerated gas-trointestinal transit time in RYGBP-operated subjects may result in an increase in GLP-1and PYY response to nutrient intake with these hormonal changes potentially contributing to reduced appetite after surgery.

In the present study,we aimed to further assess the changes in GLP-1and PYY after RYGBP.Moreover,we ex-amined the relationship between circulating GLP-1and PYY and the changes in hunger and satiety.Finally,we assessed the potential role of changes in gastric emptying and intes-tinal transit time associated with RYGBP on the hormonal response to food intake.A prospective analysis of the GLP-1 and PYY response to food intake in RYGBP-operated patients has,to our knowledge,not previously been reported.

Subjects and Methods

Study subjects

Nine obese Caucasian subjects[seven women and two men,aged 39.4?10.7yr,body mass index(BMI)47.4?6.1kg/m2]about to undergo a standardized laparoscopic RYGBP(23)were recruited from the Obesity Unit at the Hospital Cl?′nic Universitari of Barcelona.As assessed from an oral glucose tolerance test before surgery,all patients had normal glucose tolerance.Six normal-glucose-tolerant obese sub-jects matched with the experimental group for gender(four women and two men),age(41.0?10.7yr),and BMI6wk after surgery(43.6?7.9 kg/m2)were also studied.Before baseline examination,the body weight of all the participants had been stable for at least4wk.The study was approved by the hospital ethics committee,and written informed con-sent was obtained from all participants.

Study protocol

All subjects were evaluated both within8wk before RYGBP and6wk after the surgical procedure.Subjects attended the Research Facility at 0800h after overnight fasting.They were asked to avoid smoking from the night before and to refrain from strenuous exercise or alcohol in the 24h preceding the study.One subject in the RYGBP group and none in the BMI-matched group was an active smoker,and his smoking status did not change throughout the study.Subjects were weighed and mea-sured wearing light clothing,and a canula was then inserted into the distal forearm for blood sample collection.Blood was withdrawn for measurement of active GLP-1(GLP-17–36amide or GLP-17–37)and total PYY in the fasting state.Subjects consumed a250-ml standard mixed liquid meal(Isosource Energy,Novartis,Basel,Switzerland)containing 398kcal,with50%calories as carbohydrates,15%as protein,and35% as fat.The liquid formula was well tolerated by all patients even after RYGBP.Additional blood samples for GLP-1and PYY plasma concen-tration assessment were collected at10,30,60,90,and120min after meal ingestion.Serum samples were centrifuged immediately at?4C and stored at?80C until assayed.Samples from one individual obtained before and after RYGBP were assessed in the same assay.

Hormone measurements

Human active GLP-1(i.e.GLP-17–36amide or GLP-17–37)was mea-sured after extraction of plasma with ethanol using a commercial RIA (GLP-active-RIA kit,Linco Research,Inc.,St.Charles,MO).This assay uses125I-labeled GLP-17–36amide and a GLP-1antibody,which binds specifically to the N terminus of active GLP-1and does not react with total GLP-11–37,GLP-19–36,or GLP-19–37.The lowest level of active GLP-1that can be detected by this assay is3p m.The intra-and interassay coefficients of variation were31and34%,respectively.

Human plasma total PYY was measured with a commercially avail-able RIA(human-PYY-total RIA kit,Linco Research).This assay uses 125I-labeled PYY and an antibody that recognizes both the1–36and3–36 forms of human PYY.The lowest level of PYY that can be detected by this assay is4pmol/liter.The intra-and interassay coefficients of vari-ation were both less than10%.

Hunger and satiety ratings

Subjects completed a validated visual analog scale(VAS)at the same time points as blood was drawn for hormonal measurements(24).In brief,the VAS consisted of100-mm lines,and subjects were asked to make a vertical mark across the line corresponding to their feelings from 0(not at all)to100(most imaginable)hunger or satiety.Quantification was performed by measuring the distance from the left end of the line to the mark.

Gastric emptying(GE)and orocecal transit time(OCTT) In a subset of six subjects among those undergoing RYGB,GE rate and OCTT were assessed before and6wk after surgery.GE was estimated by measuring paracetamol plasma concentration after the ingestion of 1.5g paracetamol(24,25).Plasma concentrations of paracetamol were measured at0,5,10,20,30,60,90,and120min after the ingestion of the drug with the test meal.Plasma samples were stored at?80C until the analysis of paracetamol by fluorescence immunoassay(Abbott Labora-tories,Chicago,IL).The assay had an inter-and intraassay coefficient of variation of less than5%.OCTT was estimated by means of a lactulose breath test(26).After an overnight fast,subjects ingested10g lactulose syrup(Inalco Spa,Milano,Italy,packaged by Xactdose Inc.,South Beloit, IL)after a baseline breath sample had been obtained.Breath sampling then continued every15min for the first45min and every30min thereafter for a total of210min.All breath samples were analyzed immediately by a model DP Quintron gas chromatograph(Quintron Instrument Co.,Milwaukee,WI).The concentration of hydrogen was measured in parts per million,and a threshold increment of5ppm in three consecutive readings was used to establish the OCTT(26).The assay had an inter-and intraassay coefficient of variation of13and11%, respectively.

Statistical analysis

Data are expressed as mean?sd of the mean(sd)unless stated otherwise.Values for the area under the curve(AUC)for GLP-1,PYY, hunger,and satiety after a standard mixed liquid meal were calculated using the trapezoidal method.General linear model analysis with re-peated measures followed by post hoc analysis using Bonferroni was performed to evaluate the change in GLP-1or PYY after meal intake before and after surgery in the group of subjects undergoing RYGBP and the BMI-matched group.The variance homogenesis was checked by means of the Mauchly sphericity test.The Kolmogorov-Smirnov(Lil-liefors)test was used to assess the normal distribution of the residuals. Two-tailed nonparametric paired(Wilcoxon rank)or unpaired(Mann-Whitney U)tests were used to compare the hormonal response among groups.Correlations were determined by univariate linear regression (Spearman’s rank test).Statistical analysis was performed using SPSS 11.0for PC(SPSS,Inc.,Chicago,IL)with significance set at P?0.05.

Results

Plasma GLP-1and PYY concentrations

Before surgery,the ingestion of the standard liquid meal failed to induce a significant increase of either PYY or GLP-1 (Fig.1).Although the hormonal response to meal ingestion was larger for PYY,compared with GLP-1,it did not reach statistical significance(P?0.08).Six weeks after surgery, patients had lost a significant amount of weight(15.4?6.3 kg,P?0.01)but were still markedly obese(BMI41.6?5.7 kg/m2).On that second evaluation,neither fasting GLP-1nor

1736J Clin Endocrinol Metab,May2006,91(5):1735–1740Mor?′nigo et al.?GLP-1,PYY,and Gastric Bypass Surgery

fasting PYY was significantly increased,compared with pre-surgical hormonal levels (Fig.1).Remarkably,however,gen-eral linear model analysis with repeated measures showed a significant increase in the GLP-1and PYY response to meal ingestion (respectively,P ?0.05and P ?0.01).GLP-1plasma levels were significantly increased at 30and 60min after meal ingestion (Fig.1).The AUC 0–120?of the GLP-1in response to the test meal was significantly larger compared with before surgery (pre-RYGB 1704?1053vs.post-RYGB 2627?1224p m /min,P ?0.05),with this increment occurring in all but one participant (Fig.2).Likewise,6wk after surgery,plasma PYY increased promptly after food intake,reached its max-imum at 60min,and maintained similar values throughout the following hour (Fig.1).Consistently the AUC 0–120?of PYY in response to the test meal was significantly increased (pre-RYGB 3408?774vs.post-RYGB 9396?3051pmol ?liter ?1?min,P ?0.01),with that increment being ob-served in all the study subjects (Fig.2).

On postsurgical evaluation,neither the fasting nor the response to meal ingestion of GLP-1or PYY was significantly correlated with the attained BMI or the amount of weight loss.Interestingly,at this time point,the GLP-1and the PYY response to nutritional stimulation was larger than that ob-served in a group of nonoperated subjects matched with the experimental group for the BMI attained 6wk after surgery

(AUC 0–120?of GLP-11228?852p m /min,P ?0.05;AUC 0–120?of PYY 3496?877pmol ?liter ?1?min,P ?0.001).

Hunger and satiety VAS scores

Six weeks after surgery,ratings of hunger in the fasting state (P ?0.05)and after meal ingestion (AUC 0–120?,P ?0.05;Fig.3)were significantly decreased,compared with the ini-tial evaluation.Similarly,a greater postprandial satiety was reported in the operated patients after meal intake (P ?0.05,Fig.3).Six weeks after surgery,fasting GLP-1(r ?0.69;P ?0.05)and AUC 0–120?of GLP-1(r ?0.75;P ?0.05)were significantly correlated with satiety VAS in the fasting state.In contrast,we failed to find a significant correlation between fasting PYY,the maximal PYY plasma concentration,or the AUC 0–120?of PYY in response to meal ingestion and hunger and satiety VAS scores.Of note,the 1.6?1.9-fold increase in the GLP-1AUC 0–120?and the 2.9?1.2-fold increase in the PYY AUC 0–120?after meal ingestion 6wk after RYGBP were associated with a 45?86%decrease in the hunger and a 123?22%increase in the satiety AUC 0–120?ratings.How-ever,no significant correlation was found between the changes in the hormonal and behavioral parameters.

GE and OCTT

RYGBP surgery was associated with an acceleration of GE (Fig.4)and OCTT.After surgery,the time to maximal parac-etamol plasma concentration was shortened (after RYGB 6.7?2.6vs.before RYGB 19.5?6.8min;P ?0.05),and the AUC 0–60?of paracetamol significantly increased (after RYGB 1036?275vs.before RYGB 626?246pmol ?ml ?1?min;P ?0.05).Similarly,the maximal paracetamol concentration

in-

F I

G .1.Active GLP-1and total PYY in response to a liquid test meal.Active GLP-1and total PYY circulating concentrations over the course of the test (respectively,A and B)in obese subjects before (black circles ,n ?9)and 6wk after (open circles ,n ?9)RYGBP and in obese subjects matched with the experimental group for the BMI attained 6wk after surgery (open diamonds ,n ?6).Data are expressed as mean (?SEM ).a ,P ?0.05and b ,P ?0.01values are indicated for comparison relative to baseline

(Bonferroni).

F I

G .2.Individual responses of active GLP-1and total PYY after

liquid meal intake,before RYGBP,and 6wk after surgery.

Mor?′nigo et al.?GLP-1,PYY,and Gastric Bypass Surgery J Clin Endocrinol Metab,May 2006,91(5):1735–17401737

creased after surgery (before RYGB 19.5?6.8vs.after RYGB 29.6?11.5pmol/ml),although it did not reach statistical significance.Before surgery a significant increase in expira-tory hydrogen concentration after lactulose intake was ob-served at 115.0?22.4min,whereas OCTT was shortened to 75.0?24.7min 6wk after RYGBP (P ?0.05).Interestingly,after surgery the GLP-1response to meal intake was asso-ciated with a larger AUC 0–60?of paracetamol plasma con-centration (r ?0.94,P ?0.01)but not with the https://www.360docs.net/doc/859743249.html,stly,we failed to find a significant correlation between measure-ments of PYY plasma concentration and GE or OCTT esti-mates at either of the two study time points.

Discussion

This prospective study shows that RYGBP is associated with a significant increase in GLP-1and PYY response to a liquid meal 6wk after the surgical procedure,at a time at which subjects were still markedly obese.Consistent with previous reports,we observed a blunted GLP-1and PYY response to a nutrient intake (17,19,20,27–29).The signif-icantly larger GLP-1and PYY response,compared with the obese subjects with comparable BMI,suggests that the marked increase in the hindgut hormonal response was not related to the BMI attained 6wk after surgery.Nonetheless,whether the increased hormonal response was secondary to the weight loss or to the gastrointestinal anatomical changes related to RYGBP requires further studies.

Kellum et al.(18)and Meryn et al.(30)reported marked postprandial elevations in plasma enteroglucagon levels (a measure of intestinal peptides derived from proglucagon such as GLP-1)6–9months after RYGBP.Moreover,a recent cross-sectional study showed a marked increase in the GLP-1after meal intake in weight-stable RYGBP-operated subjects (19).In sharp contrast,two recent studies (31,32)failed to show a significant change in fasting GLP-1shortly after RYGBP.Nonetheless,because only the basal hormonal level was tested in these two studies,significant effects of RYGBP on the meal-induced hormonal secretion might have been overlooked.Although dietary-induced weight loss in obese subjects has been associated with an increase in GLP-1re-sponse (28),our data and that of others suggest that other mechanisms may account for the noticeable increase in the GLP-1response after RYGBP.Although a significant amount of weight loss was associated with either RYGBP or vertical banded gastroplasty (VBG),enteroglucagon response 6months after surgery was only slightly elevated in VBG-operated subjects,compared with those who underwent RYGBP (18).Similarly,postprandrial GLP-1was larger in weight-stable RYGBP-operated subjects when compared with BMI-matched subjects who had undergone gastric banding (19).

Our data are consistent with previous studies showing that RYGBP is associated with a substantial increase in post-pandrial PYY plasma concentration (19,20).In cross-sectional studies,it was shown that in weight-stable obese subjects,the PYY response to a test meal was approximately 2-to 5-fold larger after RYGBP,compared with lean and BMI-matched controls.Our prospective study further sup-ports these findings and shows that the increase in PYY response to meal ingestion occurs at an early stage after RYGBP.Despite significant weight loss,a blunted PYY re-sponse to meal intake has been reported after gastric banding (19).On the other hand,VBG and jejunoileal bypass have been associated with an increase in fasting but not postpran-dial PYY,respectively at 12months and 20yr after surgery (21,33).In sharp contrast with these results,in our and previous studies (19,20),fasting PYY was not different after RYGBP surgery.The reason for the differential PYY response among different bariatric techniques remains elusive.It has been shown that dietary-induced weight loss is associated with increased fasting PYY levels (29).However,whether weight loss is associated with changes in postprandrial

PYY

F I

G .3.Hunger and satiety VAS scores in response to a liquid test

meal.Bars represent the AUC of hunger and satiety VAS scores after meal ingestion (respectively,A and B)in obese subjects before (black bar ,n ?9)and 6wk after (open bar ,n ?9)RYGBP.Data are expressed as mean (?SEM ).a ,P ?0.05and b ,P ?0.05values are indicated for comparison between the two study time points (Wilcoxon rank

test).

F I

G .4.GE in obese subjects undergoing RYGBP.Paracetamol plasma concentration over the course of the test after the ingestion of 1.5g of paracetamol in obese subjects before (black circles ,n ?6)and 6wk after (open circles ,n ?6)RYGBP.Data are expressed as mean (?SEM ).

1738J Clin Endocrinol Metab,May 2006,91(5):1735–1740Mor?′nigo et al.?GLP-1,PYY,and Gastric Bypass Surgery

remains to be elucidated.A prospective comparison of the changes in PYY,either fasting or postpandrially,among dif-ferent treatments for obesity is warranted.

The mechanisms by which RYGB is associated with a decrease in meal frequency(6,7)are not well understood.We used VAS measurements to quantify feelings of hunger and satiety in the fasting state and throughout the standardized test meal.Our data showed that RYGBP is associated with a decreased feeling of hunger both in the fasting state and after meal intake as well as with an increased satiety after meal ingestion.These results somewhat disagree with those by Korner et al.(20)in which only a nonstatistically significant tendency toward greater satiety was found in RYGBP-oper-ated subjects,compared with BMI-matched controls.None-theless,the prospective nature of our study reinforces the validity of our findings.

Different studies have demonstrated that GLP-1and PYY may contribute to an early sense of satiety and the ability of an individual to reduce meal size.Peripherally administered GLP-1and PYY elicit satiety in healthy(15,16)and obese subjects(15,17).In that context,it is reasonable to hypoth-esize that the success of weight loss and maintenance after RYGBP could be due to decreased hunger and increased satiety induced not just by volume restriction but also by an increased hindgut hormonal response to nutrients(2,3). Consistently,the changes in GLP-1and PYY plasma con-centration after meal intake were well suited to the changes in hunger and satiety.In further support of this hypothesis, Strader et al.(22)recently showed in a rodent model that in the absence of either restriction or malabsorption ileal trans-position resulted in an increase in GLP-1and PYY plasma concentration that was associated with reduced food intake and weight loss.

Finally,we sought to address why GLP-1and PYY are elevated after RYGBP in response to a standardized liquid meal.It has been suggested that,because the surgical pro-cedure alters the physiological gastric emptying mechanism and the length of the small bowel is shortened,the change in the hormonal response could be due to an earlier contact between nutrients and the L cells located in the hindgut(2, 3,19,22).Noteworthy,the changes in gastric emptying after RYGBP surgery have seldom been reported,and,to the best of our knowledge,the OCTT in RYGBP-operated obese sub-jects has not previously been assessed.Naslund and Beck-man(34)and Horowitz et al.(35)showed no change or a slowing in gastric emptying after the ingestion of a solid meal in RYGBP-operated subjects.However,in accordance with our findings,using a scintigraphic technique Horowitz et al.

(35)showed that gastric liquid emptying occurred more rap-idly after RYGBP.The significant correlation between the AUC0–60?of paracetamol and the AUC0–60?of GLP-1after meal ingestion in our study supports the possible role of shortening in GE in the improvement of the hormonal re-sponse from the distal gut.However,the GE changes in our study should be interpreted cautiously because of the po-tentially different paracetamol pharmacokinetics between the two study time points(36).The concurrence of an in-creased hormonal response and a shortening of the OCTT6 wk after surgery in our study could be interpreted as cir-cumstantial evidence supporting that the early contact of ingested nutrients with the distal gut is associated with a marked increase in GLP-1and PYY plasma concentrations. Our data support those by Strader et al.(22)in a rodent of ileal transposition.Likewise,plasma PYY levels were markedly augmented,compared with healthy controls,in patients in whom a resection of the small intestine had been performed (37).

Our study has several limitations.First,the small sample size may not allow definite conclusions on the consequences of the changes in GLP-1and PYY plasma levels on eating patterns or its relationship with gastrointestinal motility to be drawn.Thus,further studies are needed to clarify these issues.Second,our study lacks a proper control group.In contrast with RYGBP-operated patients,the subjects in our BMI-matched group were weight-stable,nonoperated indi-viduals.A head-to-head prospective comparison between RYGBP-and GB-operated subjects would have been neces-sary to discern whether weight loss or the RYGBP is critical for the changes in the hindgut hormones.Finally,interpre-tation of the results should be cautious because of the com-mercially available assays used.The GLP-1assay had a very high coefficient of variation.The assay used to measure PYY relies on a polyclonal antibody that cross-reacts100%with the two described circulating forms of PYY,namely PYY1–36 and PYY3–36.Therefore,we measured total PYY concentra-tions rather than discriminated between two molecular iso-forms.Thus,because so far only PYY3–36has been shown to inhibit food intake in humans(16,17)and it is unclear which isoform contributed to the increased postprandial rise our patients,this may have confounded our analysis.

In summary,our data show that RYGBP is associated with a marked increase in GLP-1and PYY plasma concentrations in response to a liquid meal.However,whether weight loss or the RYGBP was critical for the changes in the hindgut hormones remains to be elucidated because our study lacks the proper control group.Moreover,we provide circumstan-tial evidence supporting the possible effect of these hindgut hormonal secretions on the changes in hunger and satiety that occur after gastric bypass surgery.Finally,our data support the hypothesis that changes in GLP-1and PYY after RYGBP could be accounted for,at least in part,by changes in gastrointestinal motility.Confirmation of these findings may lead to the development of new drugs,thereby provid-ing less invasive therapies for obesity.

Acknowledgments

We are very grateful to Leonor Sanchez for technical assistance.

Received April26,2005.Accepted February6,2006.

Address all correspondence and requests for reprints to:Dr.Josep Vidal,Obesity Unit,Endocrinology and Diabetes Department,Hospital Cl?′nic Universitari,Villarroel170,08036Barcelona,Spain.E-mail: jovidal@clinic.ub.es.

This work was supported by a grant from the Fondo de Investiga-ciones Sanitarias of the Instituto de Salud Carlos III,Red Tematica de Grupos de Obesidad(G03/028),Madrid,Spain.

The authors of this manuscript have no potential conflicts of interest to declare.

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JCEM is published monthly by The Endocrine Society(https://www.360docs.net/doc/859743249.html,),the foremost professional society serving the

endocrine community.

1740J Clin Endocrinol Metab,May2006,91(5):1735–1740Mor?′nigo et al.?GLP-1,PYY,and Gastric Bypass Surgery