Superior appetite hormone profile after equivalent weight loss bygastric bypass compared to gastric banding

M. Bose1, S. Machineni1, B. Oliván1, J. Teixeira2, J.J. McGinty2, B. Bawa1, N. Koshy2, A.Colarusso1, and B. Laferrère11New York Obesity Research Center, St. Luke's Roosevelt Hospital Center, Columbia UniversityCollege of Physicians and Surgeons, 1111 Amsterdam Avenue, New York, NY 100252Division of Bariatric Surgery, St. Luke's Roosevelt Hospital Center, Columbia University Collegeof Physicians and Surgeons, 1111 Amsterdam Avenue, New York, NY 10025

AbstractThe goal of this study was to understand the mechanisms of greater weight loss by gastric bypass(GBP) compared to gastric banding (GB) surgery. Obese weight- and age-matched subjects werestudied before (T0), after a 12 kg weight loss (T1) by GBP (n=11) or GB (n=9), and at 1 year aftersurgery (T2). PYY3-36, ghrelin, GLP-1, leptin, and amylin were measured after an oral glucosechallenge. At T1, glucose-stimulated GLP-1 and PYY levels increased significantly after GBP butnot GB. Ghrelin levels did not change significantly after either surgery. In spite of equivalent weightloss, leptin and amylin decreased after GBP, but not after GB. At T2, weight loss was greater afterGBP than GB (p=0.003). GLP-1, PYY, and amylin levels did not significantly change from T1 toT2; leptin levels continued to decrease after GBP, but not after GB at T2. Surprisingly, ghrelin AUCincreased 1 year after GBP (p=0.03). These data show that, at equivalent weight loss, favorable GLP-1and PYY changes occur after GBP, but not GB, and could explain the difference in weight loss at 1year. Mechanisms other than weight loss may explain changes of leptin and amylin after GBP.

KeywordsGLP-1; gastric bypass; weight loss; gastric banding

IntroductionBariatric surgery has become the preferred option for the treatment of morbid obesity. Gastricbypass surgery (GBP) results in about 56.7-66.5% excess weight loss, while adjustable gastricbanding (GB), a purely restrictive procedure, usually results in 40.7-54.2% excess weight loss(1). In addition to the malabsorptive and/or restrictive components of bariatric surgery, somestudies suggest that hormonal changes that occur after GBP could contribute to the betterweight loss outcome compared to GB (2-4).

Please send all correspondence to: Mousumi Bose, Ph.D., New York Obesity Research Center, Columbia University College of Physiciansand Surgeons, St. Luke's Roosevelt Hospital Center, 1111 Amsterdam Avenue, Room 1034, New York, NY 10025, P: 212.523.3357, F:212.523.4830, mb3103@columbia.edu.Disclosure Statement: This work was funded by grants from the American Diabetes Association CR-7-05 CR-18, NIH R01-DK67561,1 UL1 RR024156-03, ORC DK-26687, DERC DK-63068-05, Merck Investigator Initiated Studies Program, Amylin Investigator InitiatedStudies Program. B.L. received grant support through Merck and Amylin Investigator Initiated Studies Program in 2007. J.T is therecipient of an educational grant from Ethicon Endosurgery/ Johnson & Johnson. M.B., S.M., B.O., J.T., J.J.M., B.B., N.K., A.C., andB.L. have nothing to declare.

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Published in final edited form as:Obesity (Silver Spring). 2010 June ; 18(6): 1085–1091. doi:10.1038/oby.2009.473.

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Regulation of food intake is a complex interplay of central and peripheral signals. Somegastrointestinal hormones, such as glucagon-like peptide-1 (GLP-1), peptide YY3-36 (PYY)and ghrelin, show meal-to-meal variation, and the administration of GLP-1 (5) or PYY (6)decreases food intake. Post-prandial GLP-1 (7,8) and PYY (4,9,10) levels increase after GBPbut not after GB (11).

Reports of ghrelin levels after bariatric surgery vary widely, with reported increases (12,13),decreases (14,15), or no change after GBP, and no change or increase after GB (2,16,17).

Among other peripheral hormones associated with food intake regulation, leptin is producedin the adipocytes; leptin levels decrease with weight loss by diet (18) or by bariatric surgery,both GBP and GB (3,19). Amylin is co-secreted with insulin from the pancreas in response tonutrients; amylin analogues inhibit food intake (20,21). Circulating amylin levels decrease withdiet-induced weight loss (22).

Whether the hormonal changes after surgery are secondary to weight loss or due to the natureof the surgery is unknown. We have recently reported that at equivalent weight loss, GBPresults in greater post-prandial GLP-1 and PYY levels compared to weight loss by diet (10,23). Most longitudinal studies that have compared the hormonal changes after GBP and GBhave been conducted in patients with unmatched pre-surgery body weight, with differentialweight loss between GBP and GB groups (2,24), making the comparison between surgeriesdifficult to interpret. In this study, our goal was to compare the changes in levels of peptidesknown to regulate food intake (GLP-1, PYY, ghrelin, leptin, amylin) after GBP and GB. Inorder to differentiate the role of weight loss from that of surgery on peptide changes, we studiedthe effect of an equivalent weight loss (∼12 kg) by GBP or GB in weight-matched patients.These patients were studied again 1 year postoperatively, when weight loss was differentbetween groups. We hypothesized that some hormonal changes (post-prandial increase inGLP-1 and PYY levels, decrease in ghrelin levels) would occur after GBP but not after GB,and be directly related to the nature of the surgery, independent of weight loss; other hormones(decrease in leptin and amylin) would change similarly with equivalent weight loss after GBPand GB.

Methods and ProceduresSubjects

Obese patients who were eligible candidates for GBP, younger than 60 years of age, wereinvited to participate in the study and signed an informed consent approved by our institutionprior to enrollment. One group of patients was studied before GBP (T0), 1 month after (T1)and 1 year after GBP (T2). A second group of patients, fulfilling the same recruitment criteria,was studied before GB (T0), after a 12-kg weight loss (T1) and 1 year after surgery (T2). Therewas no time limit to achieve the matched weight loss at T1 in the GB group. GB patients werefrequently contacted by the research coordinator, who assessed weight loss and referredpatients to surgeons for band adjustment as needed. After the weight loss target of 10-12 kgwas reached after GB, patients returned for T1 studies. Glucose tolerance was assessed byhistory and/or medications, and by glucose tolerance test. Patients with type 2 diabetes for lessthan 5 years and not on insulin, thiazolidinedione, exenatide, or dipeptidyl peptidase-IV (DPP-IV) inhibitors, with HbA1c less than 8% were included in the study.

Laparoscopic bariatric surgeryFor GBP, the jejunum was divided 30 cm from the ligament of Treitz and anastomosed to a30 mL proximal gastric pouch. The jejunum was re-anastomosed 150 cm distal to thegastrojejunostomy. For GB, a silicone band (approximately 10-12 mm diameter) was placed

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around the proximal portion of the stomach to create a 30 mL pouch. This band contains avolume-adjustable balloon on its inner surface that is connected to an implantable port deviceplaced subcutaneously to allow for adjustments. Adjustments were performed by the surgeonas needed

The post-bariatric surgery nutritional recommendations included a daily intake of 600–800kcal of purée diet, 70 g protein, and 1.8 L fluid for 1 month after surgery. This was achieved,on an individual basis, with multiple small meals, snacks, and various commercial proteinsupplements. After 1 month, patients were told to introduce solid food and to increase theirdaily caloric intake to 800-1000 kcal, with 70 g protein and 1.8 L fluid daily. The diet aftersurgery was monitored by food records but not directly supervised. The diet in days precedingthe testing was not controlled for.

Three-hour OGTTAt T0, T1 and T2, all patients underwent a 3-hour 50 g (in 200 mL) oral glucose challenge(OGTT). Patients were fasted for 12 hours prior to testing. After intravenous catheter insertionat 0800 hours, blood samples were collected before and at 15, 30, 45, 60, 90, 120, and 180minutes following the glucose drink, on chilled EDTA tubes with added aprotinin (500kallikrein inhibitory U/mL blood) and DPP-IV inhibitor (Millipore Corp., St. Charles, MO)(10 μl/mL blood). Samples were then centrifuged at 4° C for plasma collection before storageat −70° C.

AssaysPYY3-36, total ghrelin, total GLP-1, leptin, and amylin were measured by radio-immunoassay(RIA) (Millipore, St. Charles, MO). All intra- and inter-assay coefficients of variance rangedfrom 3.4-7.4% and 4.4-7.4 %, respectively. Glucose concentration was measured at bedsideby the glucose oxidase method (Beckman glucose analyzer; Beckman Coulter, Inc., Fullerton,CA). All hormonal and metabolite assays were performed at the New York Obesity ResearchCenter.

Statistical AnalysesTotal areas under the curve 0-180′ (AUC) for outcome variables were calculated using thetrapezoidal method. Differences between surgical groups were assessed by unpaired t-test.General linear model (GLM) with repeated measures was used to detect changes over 1 yearwithin each surgical group. Simple bivariate correlation analyses were performed betweenweight loss and outcome variables. Data are expressed as mean ± SD except in figures wheremean ± SEM are reported. Statistical significance was set at p<0.05 (2-tailed). Statisticalanalyses were performed with SPSS 16.0 (SPSS Inc., Chicago, IL).

ResultsBaseline characteristics (T0)

At T0, before surgery, patients in the GBP and GB groups had similar body weight, BMI,fasting leptin, amylin, glucose, insulin, GLP-1, PYY and ghrelin levels, and glucose-stimulatedGLP-1, PYY, ghrelin, and amylin levels (Table 1). Most patients were either diabetic or glucoseintolerant (11 in GBP group, 6 in GB group); the remaining 3 patients (GB group) werenormoglycemic. Hemoglobin A1C (HbA1C) levels were significantly higher in the GBP groupcompared to the GB group at baseline (6.7±0.8% vs. 5.7±0.7%, p=0.01).

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Band adjustmentIn the first year after GB, patients returned for a total of 6.5±1.0 follow-up visits (range 5-8)and received 2.0±2.1 band adjustments (range 0-6).

Equivalent weight loss (T1)GBP patients were studied before and about 1 month after surgery (T1 for GBP = 39.6±20.6days, range 22-92 days) with a mean weight loss of 13.3±6.4 kg (range 5.3 -24.9 kg, Table 2).GB patients were studied after a matched weight loss of 11.3±2.5 kg (range 8.9-17.2 kg, p=0.35compared to GBP, Table 2), which was achieved after about 3 months (T1 for GB = 97.4±84.3days, range 21-235 days, p=0.08 compared to GBP).

Fasting GLP-1 and PYY levels did not change significantly after either surgery (Table 2, Figure1a-b) and were not significantly different between surgical groups. GLP-1 and PYY levels(AUC) significantly increased from baseline after oral glucose after GBP (Table 2, Figure 1a-b) but not after GB. The change in GLP-1 and PYY AUC from baseline was significantlydifferent between the GBP and GB groups (GLP-1: p<0.001; PYY: p=0.018, Table 2).

Fasting and glucose-suppressed ghrelin levels tended to decrease after GBP and increase afterGB, but neither ghrelin values at T1 nor the changes from baseline were significantly differentbetween groups (Table 2, Figure 2a-b).

Fasting leptin levels decreased after GBP (p=0.0001) but not after GB (Table 2, Figure 2c).However, neither the leptin values at T1 nor the changes from baseline were significantlydifferent between surgical groups. The decreases in fasting amylin and amylin AUC duringthe OGTT at T1 were significantly greater after GBP than GB (p=0.028 and p=0.026 for fastingamylin and amylin AUC, respectively, Table 2).

One year post-surgery (T2)One year after surgery, both groups continued to lose weight. Patients after GBP lost almosttwice as much weight as patients after GB (36.4±11.0 kg vs. 17.8±12.7 kg, p=0.01), althoughthe range in each group varied (23.6-63.8 kg for GBP and 0.10-40.6 kg for GB) (Table 3).HbA1C decreased significantly after GBP but was not different between GBP and GB groups1 year after surgery (5.2±0.4% vs. 5.5±0.6%, respectively, p=0.13).

Fasting and glucose-stimulated levels of GLP-1 and PYY remained unchanged from T1 to T2in GBP patients, with sustained elevation of glucose-stimulated GLP-1 (3-fold increase) andPYY (60% increase) levels (Table 3, Figure 1a-b). In spite of additional weight loss after GB,neither fasting nor glucose-stimulated GLP-1 and PYY levels changed at T2. As a result, thechanges in glucose stimulated GLP-1 and PYY from baseline to T2 was significantly differentbetween the GBP and GB group (GLP-1: p=0.002; PYY: p=0.002, Table 3).

Fasting and glucose-suppressed ghrelin AUC significantly increased by 46% from T1 to T2after GBP (p<0.05, Table 3, Figure 2a and 2b). After GB, fasting and glucose-suppressedghrelin levels continued to increase non-significantly at T2 (Table 3, Figure 2a and 2b). At T2,despite the greater amount of weight loss after GBP compared to GB, neither ghrelin levelsnor the changes from baseline were significantly different between the 2 groups (Table 4).

Although patients in both groups continued to lose weight at T2 compared to T0, leptin levelscontinued to decrease significantly only after GBP, and did not change after GB (Figure 2c).Both the leptin values at T2 and the change in leptin from baseline to T2 was significantlydifferent between the 2 surgical groups (p=0.04 for both comparisons, Table 3).

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At 1 year, fasting and glucose-stimulated amylin levels continued to decrease nonsignificantlyand were not different between surgical groups (Table 3).

DiscussionWe studied hormonal signals relating to food intake after GBP and GB, as potentialmechanisms for the greater weight loss after GBP. In order to distinguish between the surgery-related hormonal effects from the weight loss-related effects, we prospectively compared thechanges of these hormonal signals following GBP and GB, first after a matched 12 kg weightloss, and then at 1 year, at differential weight loss.

GBP has been shown to consistently produce greater weight loss than GB (25,26); this effectis supported in our data at 1 year. Nevertheless, some studies suggest that by 3 to 7 years post-surgery, weight loss tends to be similar between surgical groups (27). The mechanisms ofsustained weight loss after these two surgeries are not yet known.

Our data confirm, as previously shown, a rapid and substantial rise of GLP-1 (7,23) and PYY(10) 1 month after GBP, but not after equivalent weight loss by GB. In contrast to previousstudies, either cross-sectional or performed under different weight loss conditions betweengroups (11,24), our patients were matched at baseline for both body weight and endocrineparameters. These results suggest that the dramatic increase in GLP-1 and PYY after GBP, butnot after GB or diet (10,23), is likely related to the nature of the bypass surgery itself, and notto the weight loss. The post-prandial increase in GLP-1 and PYY 1 month after GBP remainsunchanged 1 year after surgery, despite continued weight loss. This further supports the ideathat the gut peptide increases are independent of weight loss and related to the GBP procedure.

A recent study by de Carvalho et al. (28) reported that glucose-stimulated GLP-1 levels 9months after GBP were nonsignificantly higher in patients with pre-operative diabetes orglucose intolerance compared to normoglycemic patients. This finding suggests that thedifferences in glucose-stimulated GLP-1 levels between the 2 surgical groups may beattributable to differences in glucose tolerance status between the GBP and GB groups.However, the magnitude of the change in GLP-1 levels between the 2 surgical groups in ourstudy is considerably greater (10-fold) compared to the change between the glucose intolerantand normoglycemic group observed in the study by de Carvalho et al. (28). This supports theidea that the changes that we observed in GLP-1 and PYY levels between the GBP and GBgroups are primarily due to the surgical differences and are most likely minimally affected bythe slight differences in glucose tolerance status between the 2 groups.

Both GLP-1 and PYY administration reduce food intake in animal models and in humans (5,29), an effect mediated by gut vagal afferents (30), or ligand-receptor interactions in thehypothalamus (31). Nonspecific blockade of GLP-1 and PYY with octreotide after GBP or GBdecreased satiety and increased meal size (32). A recent study reported that brain activationchanges after a peripheral administration of PYY3-36 decreases food intake in humans (33),further characterizing the role of gut-brain interactions and their effects on energy intake.

PYY administration decreases adiposity in rats (34), and weekly subcutaneous administrationof a long-acting GLP-1 analogue for 15 weeks significantly reduced body weight in obesediabetic patients compared to placebo (35). It is possible that the increase in GLP-1 and PYYafter GBP may be, independently and/or additively, partially responsible for its weight losseffects, via meal-to-meal regulation.

Ghrelin is the only peripheral peptide known to stimulate food intake (36,37). The decrease ofghrelin levels (14,15), or the absence of elevation of ghrelin levels (3), often reported afterGBP, are believed to contribute to the weight loss effects after this surgery. Our data confirm

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this rapid effect of GBP on the decrease of ghrelin levels, in spite of a 12 kg weight loss, 1month after the surgery. However, surprisingly, ghrelin levels increased with further weightloss 1 year after GBP. This is in agreement with another study (38). It is possible that temporaryvagal dysfunction results in the initial decrease of ghrelin levels after GBP, with a subsequentincrease as a function of weight loss. The late increase one year after GBP is similar to thatseen after weight loss by diet and GB (2,14). The discrepancy between our study and others(2,14,24) on ghrelin levels immediately after GBP may be related to the status of energy balanceof the patients, the alteration of the vagal nerve, possible Helicobacter pylori-related infections,or the diet composition and frequency of meals of the subjects prior to measurement (12,16,38).

Leptin is secreted from the adipocytes in proportion to fat mass; its primary function is to actcentrally on the hypothalamus to reduce food intake (39). Leptin levels consistently decreasewith various modes of weight loss, including diet (18), GB (17), and GBP (19). Interestingly,our data show that an equivalent 12 kg weight loss decreases leptin levels after GBP but notafter GB. In addition, the change in leptin levels after either surgery at both T1 and T2 did notcorrelate to weight loss (data not shown), as shown in previous studies (17,24). This findingsuggests that changes in leptin after GBP may be partially related to the nature of the surgery,although the role of caloric restriction, changes in body fat composition and the large variabilityin this small sample size cannot be ruled out. One can speculate that lower leptin levels afterGBP may indicate reduced leptin resistance (40) and a lower threshold necessary to induce areduction in food intake. One year after surgery, leptin levels decreased further after GBP withcontinued weight loss, but not after GB, despite significant and continued weight loss. Onelimitation of this study is that body composition and fat mass were not measured. As fat massis a stronger predictor of leptin levels compared to body weight, it is possible that a minimalreduction in body fat mass after GB is responsible for the lack of change in leptin levels.However, many studies have reported a significant reduction in fat mass one year after GB(41-43), suggesting that leptin levels would also decrease after this surgery. It will be interestingto see if these differential effects persist in a larger group when all subjects are at weightmaintenance.

Amylin is co-secreted with insulin from the pancreas. In addition to its effects on glycemiccontrol, administration of amylin analogues reduce food intake (20,21), and one study showedthat circulating amylin levels were reduced after a diet-induced weight loss in a population ofobese nondiabetic children (22). We report that fasting and postprandial amylin levelsdecreased after GBP and did not change after GB, following a 12 kg weight loss. To ourknowledge this is the first report on the changes in amylin levels after bariatric surgery. GBpatients exhibited a non-significant decrease in fasting and glucose-stimulated amylin levels,implying that weight loss may also contribute to the reduction in amylin levels. It cannot,however, be ruled that the differences in amylin changes between the 2 surgical groups is dueto the slight differences in glucose tolerance status. As amylin is co-secreted with insulin,reduced insulin secretion after GBP may account for some of the changes observed in amylinlevels. Insulin AUC decreased non-significantly after GBP (data not shown). Interestingly, thepattern of amylin levels in response to an OGTT mirrors previously reported changes observedwith insulin, C-peptide and pro-insulin levels after GBP (7).

Although the absence of an effect of GB on stimulated GLP-1 and PYY levels was expected,our data surprisingly showed no change in ghrelin, leptin, and amylin levels after GB, despitesignificant weight loss. The results in this study suggest that hormonal signals related to foodintake do not play a major role in the weight loss effects of GB. However, it is possible thatour small study group may not have given us enough power to detect a significant change inthese hormone levels after GB. Larger clinical trials will confirm whether or not there arehormonal changes that occur after GB and if these changes contribute to its weight loss effects.

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A limitation of our study is that we did not measure food intake. Food intake measurementsby food records are often inconsistent (44) and in the laboratory can be particularly challengingafter bariatric surgery, due to the size of the pouch and or the level of band adjustment. Hungerand satiety, assessed by visual analogue scale, has been studied after bariatric surgery (8,45),showing a decrease in hunger and increase in satiety after GBP, but no correlation with gutpeptide levels. Unfortunately these measures are not sensitive enough in a small group ofpatients (45) and do not always correlate with food intake (46). More long term studies (>1year post surgery) may be able to clearly determine whether the changes in hormone levels doindeed relate to changes in food intake after GBP and GB.

If one postulates that the increase in GLP-1 and PYY and the decrease in leptin and amylinmay participate in the decrease food intake after GBP, these changes should predict futureweight loss. However, we found no correlations between fasting or stimulated hormone levels,with body weight or weight loss at one year (data not shown); the small number of patientsmay not provide enough power to observe such correlations. Another beneficial effect of gutpeptide changes, specifically GLP-1, may be related to glucose homoeostasis after GBP. Arecent study in rats reported blunted glucose tolerance in diabetic Goto-Kakizaki rats treatedwith exendin-9, a GLP-1 antagonist after duodenal jejunal bypass surgery (47). Whether thechanges in gut hormones, which may modify appetite and food intake (32), also affect energybalance and body weight after GBP remains to be demonstrated.

Concluding remarksOur study confirms that the changes of the gut hormones GLP-1 and PYY are consistent andof large magnitude after GBP. Although it is tempting to assume a role of these gut peptidechanges in the sustained weight loss after GBP, studies to date remain purely associative. Theuse of specific gut hormone receptor agonists and antagonists in studies such as these mayprovide categorical evidence as to the potential hormonal mechanisms of appetite control, mealregulation, and weight loss after GBP.

Our study demonstrates the importance of well-controlled longitudinal studies to interpret thedifferential changes of ghrelin after GBP. Our data suggest that the early and late changes inghrelin levels may occur by different mechanisms.

GB is a powerful tool to achieve weight loss in morbidly obese patients, yet its mechanism ofaction remains unknown and is likely not mediated by changes in gut peptides. Our data showunexpectedly that leptin and ghrelin did not respond to weight change after GB. Future studiesassessing daily meal composition, size, and frequency, and body composition after surgerywill help determine mechanisms of weight loss after various types of bariatric surgery.

AcknowledgmentsThis work was funded by grants from the American Diabetes Association CR-7-05 CR-18, NIH R01-DK67561, GCRC1 UL1 RR024156-02, ORC DK-26687, DERC DK-63068-05, and NIH T32-DK07559. We would like to thank ourvolunteer participants, the CRC team, Ping Zhou and Yim Dam for their technical help, and Sara Arias and NicholasSwerdlow for assistance in manuscript preparation.

References1. Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery: a systematic review and meta-analysis.

Jama 2004;292:1724–37. [PubMed: 15479938]2. Stoeckli R, Chanda R, Langer I, Keller U. Changes of body weight and plasma ghrelin levels after

gastric banding and gastric bypass. Obes Res 2004;12:346–50. [PubMed: 14981228]3. Korner J, Inabnet W, Conwell IM, et al. Differential effects of gastric bypass and banding on circulating

gut hormone and leptin levels. Obesity (Silver Spring) 2006;14:1553–61. [PubMed: 17030966]

Bose et al. Page 7

Obesity (Silver Spring). Author manuscript; available in PMC 2011 June 1.

NIH

-PA Author Manuscript

NIH

-PA Author Manuscript

NIH

-PA Author Manuscript

4. le Roux CW, Aylwin SJ, Batterham RL, et al. Gut hormone profiles following bariatric surgery favoran anorectic state, facilitate weight loss, and improve metabolic parameters. Ann Surg 2006;243:108–14. [PubMed: 16371744]

5. Naslund E, Gutniak M, Skogar S, Rossner S, Hellstrom PM. Glucagon-like peptide 1 increases theperiod of postprandial satiety and slows gastric emptying in obese men. Am J Clin Nutr 1998;68:525–30. [PubMed: 9734726]

6. Batterham RL, Cohen MA, Ellis SM, et al. Inhibition of food intake in obese subjects by peptideYY3-36. N Engl J Med 2003;349:941–8. [PubMed: 12954742]

7. Laferrère B, Heshka S, Wang K, et al. Incretin levels and effect are markedly enhanced 1 month afterRoux-en-Y gastric bypass surgery in obese patients with type 2 diabetes. Diabetes Care 2007;30:1709–16. [PubMed: 17416796]

8. Morinigo R, Moize V, Musri M, et al. Glucagon-like peptide-1, peptide YY, hunger, and satiety aftergastric bypass surgery in morbidly obese subjects. J Clin Endocrinol Metab 2006;91:1735–40.[PubMed: 16478824]

9. Morinigo R, Vidal J, Lacy AM, Delgado S, Casamitjana R, Gomis R. Circulating peptide YY, weightloss, and glucose homeostasis after gastric bypass surgery in morbidly obese subjects. Ann Surg2008;247:270–5. [PubMed: 18216532]

10. Olivan B, Teixeira J, Bose M, et al. Effect of weight loss by diet or gastric bypass surgery on peptideYY3-36 levels. Ann Surg 2009;249:948–53. [PubMed: 19474685]

11. Rodieux F, Giusti V, D'Alessio DA, Suter M, Tappy L. Effects of gastric bypass and gastric bandingon glucose kinetics and gut hormone release. Obesity (Silver Spring) 2008;16:298–305. [PubMed:18239636]

12. Faraj M, Havel PJ, Phelis S, Blank D, Sniderman AD, Cianflone K. Plasma acylation-stimulatingprotein, adiponectin, leptin, and ghrelin before and after weight loss induced by gastric bypass surgeryin morbidly obese subjects. J Clin Endocrinol Metab 2003;88:1594–602. [PubMed: 12679444]

13. Holdstock C, Engstrom BE, Ohrvall M, Lind L, Sundbom M, Karlsson FA. Ghrelin and adipose tissueregulatory peptides: effect of gastric bypass surgery in obese humans. J Clin Endocrinol Metab2003;88:3177–83. [PubMed: 12843162]

14. Cummings DE, Weigle DS, Frayo RS, et al. Plasma ghrelin levels after diet-induced weight loss orgastric bypass surgery. N Engl J Med 2002;346:1623–30. [PubMed: 12023994]

15. Morinigo R, Casamitjana R, Moize V, et al. Short-term effects of gastric bypass surgery on circulatingghrelin levels. Obes Res 2004;12:1108–16. [PubMed: 15292475]

16. Fruhbeck G, Rotellar F, Hernandez-Lizoain JL, et al. Fasting plasma ghrelin concentrations 6 monthsafter gastric bypass are not determined by weight loss or changes in insulinemia. Obes Surg2004;14:1208–15. [PubMed: 15527636]

17. Shak JR, Roper J, Perez-Perez GI, et al. The Effect of Laparoscopic Gastric Banding Surgery onPlasma Levels of Appetite-Control, Insulinotropic, and Digestive Hormones. Obes Surg. 2008

18. Geldszus R, Mayr B, Horn R, Geisthovel F, von zur Muhlen A, Brabant G. Serum leptin and weightreduction in female obesity. Eur J Endocrinol 1996;135:659–62. [PubMed: 9025708]

19. Geloneze B, Tambascia MA, Pareja JC, Repetto EM, Magna LA, Pereira SG. Serum leptin levelsafter bariatric surgery across a range of glucose tolerance from normal to diabetes. Obes Surg2001;11:693–8. [PubMed: 11775566]

20. Smith SR, Blundell JE, Burns C, et al. Pramlintide treatment reduces 24-h caloric intake and mealsizes and improves control of eating in obese subjects: a 6-wk translational research study. Am JPhysiol Endocrinol Metab 2007;293:E620–7. [PubMed: 17505051]

21. Chapman I, Parker B, Doran S, et al. Low-dose pramlintide reduced food intake and meal durationin healthy, normal-weight subjects. Obesity (Silver Spring) 2007;15:1179–86. [PubMed: 17495194]

22. Reinehr T, de Sousa G, Niklowitz P, Roth CL. Amylin and its relation to insulin and lipids in obesechildren before and after weight loss. Obesity (Silver Spring) 2007;15:2006–11. [PubMed:17712118]

23. Laferrère B, Teixeira J, McGinty J, et al. Effect of weight loss by gastric bypass surgery versushypocaloric diet on glucose and incretin levels in patients with type 2 diabetes. J Clin EndocrinolMetab. 2008

Bose et al. Page 8

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NIH

-PA Author Manuscript

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-PA Author Manuscript

24. Korner J, Inabnet W, Febres G, et al. Prospective study of gut hormone and metabolic changes afteradjustable gastric banding and Roux-en-Y gastric bypass. Int J Obes (Lond). 2009

25. Angrisani L, Lorenzo M, Borrelli V. Laparoscopic adjustable gastric banding versus Roux-en-Ygastric bypass: 5-year results of a prospective randomized trial. Surg Obes Relat Dis 2007;3:127–32. discussion 32-3. [PubMed: 17331805]

26. Tice JA, Karliner L, Walsh J, Petersen AJ, Feldman MD. Gastric banding or bypass? A systematicreview comparing the two most popular bariatric procedures. Am J Med 2008;121:885–93. [PubMed:18823860]

27. O'Brien PE, McPhail T, Chaston TB, Dixon JB. Systematic review of medium-term weight loss afterbariatric operations. Obes Surg 2006;16:1032–40. [PubMed: 16901357]

28. de Carvalho CP, Marin DM, de Souza AL, et al. GLP-1 and adiponectin: effect of weight loss afterdietary restriction and gastric bypass in morbidly obese patients with normal and abnormal glucosemetabolism. Obes Surg 2009;19:313–20. [PubMed: 18815849]

29. Batterham RL, Cowley MA, Small CJ, et al. Gut hormone PYY(3-36) physiologically inhibits foodintake. Nature 2002;418:650–4. [PubMed: 12167864]

30. Abbott CR, Monteiro M, Small CJ, et al. The inhibitory effects of peripheral administration of peptideYY(3-36) and glucagon-like peptide-1 on food intake are attenuated by ablation of the vagal-brainstem-hypothalamic pathway. Brain Res 2005;1044:127–31. [PubMed: 15862798]

31. Cummings DE, Overduin J. Gastrointestinal regulation of food intake. J Clin Invest 2007;117:13–23. [PubMed: 17200702]

32. le Roux CW, Welbourn R, Werling M, et al. Gut hormones as mediators of appetite and weight lossafter Roux-en-Y gastric bypass. Ann Surg 2007;246:780–5. [PubMed: 17968169]

33. Batterham RL, ffytche DH, Rosenthal JM, et al. PYY modulation of cortical and hypothalamic brainareas predicts feeding behaviour in humans. Nature 2007;450:106–9. [PubMed: 17934448]

34. Reidelberger RD, Haver AC, Chelikani PK, Buescher JL. Effects of different intermittent peptideYY (3-36) dosing strategies on food intake, body weight, and adiposity in diet-induced obese rats.Am J Physiol Regul Integr Comp Physiol 2008;295:R449–58. [PubMed: 18550871]

35. Kim D, MacConell L, Zhuang D, et al. Effects of once-weekly dosing of a long-acting releaseformulation of exenatide on glucose control and body weight in subjects with type 2 diabetes.Diabetes Care 2007;30:1487–93. [PubMed: 17353504]

36. Cummings DE, Purnell JQ, Frayo RS, Schmidova K, Wisse BE, Weigle DS. A preprandial rise inplasma ghrelin levels suggests a role in meal initiation in humans. Diabetes 2001;50:1714–9.[PubMed: 11473029]

37. Druce MR, Wren AM, Park AJ, et al. Ghrelin increases food intake in obese as well as lean subjects.Int J Obes (Lond) 2005;29:1130–6. [PubMed: 15917842]

38. Sundbom M, Holdstock C, Engstrom BE, Karlsson FA. Early changes in ghrelin following Roux-en-Y gastric bypass: influence of vagal nerve functionality? Obes Surg 2007;17:304–10. [PubMed:17546836]

39. Pelleymounter MA, Cullen MJ, Baker MB, et al. Effects of the obese gene product on body weightregulation in ob/ob mice. Science 1995;269:540–3. [PubMed: 7624776]

40. Jequier E, Tappy L. Regulation of body weight in humans. Physiol Rev 1999;79:451–80. [PubMed:10221987]

41. Pontiroli AE, Pizzocri P, Librenti MC, et al. Laparoscopic adjustable gastric banding for the treatmentof morbid (grade 3) obesity and its metabolic complications: a three-year study. J Clin EndocrinolMetab 2002;87:3555–61. [PubMed: 12161474]

42. Savastano S, Angrisani L, Di Somma C, et al. Relationship Between Growth Hormone/Insulin-LikeGrowth Factor-1 Axis Integrity and Voluntary Weight Loss After Gastric Banding Surgery for SevereObesity. Obes Surg. 2009

43. Heath ML, Kow L, Slavotinek JP, Valentine R, Toouli J, Thompson CH. Abdominal adiposity andliver fat content 3 and 12 months after gastric banding surgery. Metabolism 2009;58:753–8.[PubMed: 19375765]

44. Todd KS, Hudes M, Calloway DH. Food intake measurement: problems and approaches. Am J ClinNutr 1983;37:139–46. [PubMed: 6849275]

Bose et al. Page 9

Obesity (Silver Spring). Author manuscript; available in PMC 2011 June 1.

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-PA Author Manuscript

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45. Korner J, Bessler M, Cirilo LJ, et al. Effects of Roux-en-Y gastric bypass surgery on fasting andpostprandial concentrations of plasma ghrelin, peptide YY, and insulin. J Clin Endocrinol Metab2005;90:359–65. [PubMed: 15483088]

46. Pi-Sunyer X, Kissileff HR, Thornton J, Smith GP. C-terminal octapeptide of cholecystokinindecreases food intake in obese men. Physiol Behav 1982;29:627–30. [PubMed: 6294699]

47. Kindel TL, Yoder SM, Seeley RJ, D'Alessio DA, Tso P. Duodenal-Jejunal Exclusion ImprovesGlucose Tolerance in the Diabetic, Goto-Kakizaki Rat by a GLP-1 Receptor-Mediated Mechanism.J Gastrointest Surg. 2009

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Figure 1.Mean post-prandial GLP-1 (a) and PYY (b) levels at T0, T1, and T2 after GBP or GB. Dataare present as mean ± S.E.M. GLP-1, Glucagon-like peptide-1; PYY, peptide YY; T0, baseline;T1, at equivalent weight loss (12 kg) between surgical groups; T2, at one year post-surgery;GBP, gastric bypass; GB, gastric banding.

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Figure 2.Mean fasting ghrelin (a), ghrelin AUC (b), and leptin (c) T0, T1, and T2 after GBP or GB.Data are present as mean ± S.E.M. Statistical signficance is indicated with an asterisk (*)between groups only AUC, area under the curve; T0, baseline; T1, at equivalent weight loss(12 kg) between surgical groups; T2, at one year post-surgery; GBP, gastric bypass; GB, gastricbanding.

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Table 1

Subject characteristics at baselinea

GBP (n=11) GB (n=9)

Weight (kg) 116.1± 19.6 125.2± 19.9

BMI (kg/m2) 45.1±8.2 46.5±6.8

Fasting GLP-1T (pmol/L) 6.8±4.3 4.9±1.9

GLP-1T Peak (pmol/L) 15.5±5.9 11.9±5.4

GLP-1T AUC (pmol/L/min) 7.2±3.0 4.8±1.2§

Fasting PYY (pmol/L) 60.7 ±21.2 46.0±25.6

Peak PYY (pmol/L) 74.3 ±26.0 52.3 ±24.9

PYY AUC (pmol/L) 50.5±27.3 35.7±21.4

Fasting Ghrelin (pmol/L) 148.2±36.8 120.3±32.6

Ghrelin Nadir (pmol/L) 126.1±38.8 93.7±33.2

Ghrelin AUC (pmol/L/min) 139.3±40.4 111.9±30.2

Fasting Leptin (ng/mL) 34.1±9.7 30.4±9.1

Fasting Amylin (pmol/L) 14.5±9.5 20.6±25.8

Amylin AUC (pmol/L/min) 19.9±9.3 23.6±22.9

aSection symbol (§) indicates significantly different from GBP (p<0.05, unpaired t-test)

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Tabl

e 2

Cha

nges

in w

eigh

t, G

LP-1

, PY

Y, g

hrel

in, l

eptin

, and

am

ylin

afte

r equ

ival

ent w

eigh

t los

s (T1

) by

GB

P or

GB

a

GB

P (n

=11)

GB

(n=9

)

Bas

elin

ePo

st-w

eigh

t los

s (T

1)Δ

Bas

elin

ePo

st-w

eigh

t los

s (T

1)Δ

Wei

ght (

kg)

118.

3±18

.910

5.1±

18.

4*-1

3.3±

6.4

122.

9±20

.611

1.7±

20.7

*-1

1.3±

2.5

BM

I (kg

/m2 )

45.1

±7.8

40.1

± 6.

8*-5

.0±2

.245

.7±7

.541

.4±

7.3*

-4.2

±1.1

Fast

ing

GL

P-1T

(pm

ol/L

)6.

8±4.

37.

0±3.

30.

2±4.

24.

9±1.

94.

2±1.

1§-0

.6±2

.3

GL

P-1T

Pea

k (p

mol

/L)

15.5

±5.9

102.

3 ±5

6.1*

86.8

±57.

111

.9±5

.417

.5 ±

18.7

§5.

6±19

.7§

GL

P-1T

AU

C (p

mol

/L/m

in)

7.2±

3.0

29.0

±9.9

*21

.8±9

.74.

8±1.

2§6.

3±4.

7§1.

5±5.

1§

Fast

ing

PYY

(pm

ol/L

)60

.7 ±

21.2

48.2

±31

.2-1

2.6

±23.

846

.0±2

5.6

46.8

±11

.40.

9±17

.0

Peak

PY

Y (p

mol

/L)

74.3

±26

.012

4.9

±50.

4*50

.6 ±

40.5

52.3

±24

.959

.7 ±

19.4

§7.

4 ±2

1.5§

PYY

AU

C (p

mol

/L/m

in)

50.5

±27.

384

.4±3

2.6*

33.9

±28.

735

.7±2

1.4

41.2

±13.

1§5.

5±17

.2§

Fast

ing

Ghr

elin

(pm

ol/L

)14

8.2±

36.8

135.

3±64

.3-1

2.9±

46.5

120.

3±32

.613

6.7±

56.3

16.3

±36.

9

Ghr

elin

Nad

ir (p

mol

/L)

126.

1±38

.810

5.5±

45.2

-20.

7±29

.593

.7±3

3.2

99.8

±49.

16.

1±27

.8

Ghr

elin

AU

C (p

mol

/L/m

in)

139.

3±40

.412

3.6±

49.9

-15.

8 ±3

2.2

111.

9±30

.212

0.9±

43.0

9.1±

28.6

Fast

ing

Lep

tin (n

g/m

L)

34.1

±9.7

18.3

±7.

9*-1

5.7

±6.3

30.4

±9.1

22.3

± 6.

6-8

.1 ±

11.7

Fast

ing

Am

ylin

(pm

ol/L

)14

.5±9

.56.

4± 6

.3*

-8.1

±6.4

20.6

±25.

826

.7±

35.2

6.1±

14.3

§

Am

ylin

AU

C (p

mol

/L/m

in)

19.9

±9.3

9.5±

5.2*

-10.

4±9.

723

.6±2

2.9

27.0

± 27

.82.

5±12

.0§

a Ast

eris

k (*

) ind

icat

es si

gnifi

cant

ly d

iffer

ent f

rom

bas

elin

e (p

<0.0

5, G

LM w

ith re

peat

ed m

easu

res)

. Sec

tion

sym

bol (

§) in

dica

tes s

igni

fican

tly d

iffer

ent f

rom

GB

P (p

<0.0

5, u

npai

red

t-tes

t)

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Tabl

e 3

Cha

nges

in w

eigh

t, G

LP-1

, PY

Y, g

hrel

in, l

eptin

, and

am

ylin

by

GB

P or

GB

afte

r 1 y

ear (

T2)a

GB

P (n

=11)

GB

(n=9

)

Bas

elin

eA

fter

1 ye

ar (T

2)Δ

Bas

elin

eA

fter

1 ye

ar (T

2)Δ

Wei

ght (

kg)

118.

3±18

.981

.9±

13.0

*-3

6.4±

10.

912

2.9±

20.6

105.

1±18

.4*§

-17.

8± 1

2.7

§

BM

I (kg

/m2 )

45.1

±7.8

31.4

±4.6

*-1

3.7±

4.7

45.7

±7.5

39.8

± 6.

9* §

-6.9

±2.4

Fast

ing

GL

P-1T

(pm

ol/L

)6.

8±4.

38.

5±11

.11.

6±9.

34.

9±1.

94.

0±2.

0-0

.9±1

.4

GL

P-1T

Pea

k (p

mol

/L)

15.5

±5.9

127.

5 ±8

3.5*

112.

0± 8

6.7

11.9

±5.4

9.4±

8.2§

-2.6

±8.5

a

GL

P-1T

AU

C (p

mol

/L/m

in)

7.2±

3.0

26.4

±15

.8*

19.2

±16.

74.

8±1.

2§3.

8±0.

9§-1

.0±1

.5§

Fast

ing

PYY

(pm

ol/L

)60

.7 ±

21.2

66.9

±23

.06.

2 ±2

3.3

46.0

±25.

636

.3 ±

13.1

§-9

.6±2

0.5

Peak

PY

Y (p

mol

/L)

74.3

±26

.012

0.6

±38.

6*46

.3 ±

35.3

52.3

±24

.944

.2 ±

14.8

§-8

.1 ±

25.0

PYY

AU

C (p

mol

/L/m

in)

50.5

±27.

327

.8±8

.8*

-7.9

±21.

735

.7±2

1.4

27.8

±8.8

§-7

.9±2

1.7§

Fast

ing

Ghr

elin

(pm

ol/L

)14

8.2±

36.8

211.

7±92

.163

.4±7

1.1

120.

3±32

.614

7.8±

55.8

27.5

±48.

3

Ghr

elin

Nad

ir (p

mol

/L)

126.

1±38

.815

0.5±

48.0

24.3

±28.

193

.7±3

3.2

120.

2±44

.526

.5±3

5.7

Ghr

elin

AU

C (p

mol

/L/m

in)

139.

3±40

.417

9.8±

57.

9*40

.5±3

4.9

111.

9±30

.213

2.3

±46.

320

.5±4

0.4

Fast

ing

Lep

tin (n

g/m

L)

34.1

±9.7

13.4

± 7.

1*-2

0.7±

7.3

30.4

±9.1

22.9

±11

.3§

-7.5

±15

.7§

Fast

ing

Am

ylin

(pm

ol/L

)14

.5±9

.53.

7±3.

4*-1

0.7±

7.4

20.6

±25.

817

.8±

23.2

-2.8

±16.

7

Am

ylin

AU

C (p

mol

/L/m

in)

19.9

±9.3

7.0±

3.1*

-12.

9±8.

323

.6±2

2.9

17.4

±23.

7-3

.4±1

5.9

a Ast

eris

k (*

) ind

icat

es si

gnifi

cant

ly d

iffer

ent f

rom

bas

elin

e (p

<0.0

5, G

LM w

ith re

peat

ed m

easu

res)

. Sec

tion

sym

bol (

§) in

dica

tes s

igni

fican

tly d

iffer

ent f

rom

GB

P (p

<0.0

5, u

npai

red

t-tes

t)

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Table 4

Summary of changes in hormones after GBP and GBa

Equivalent weight loss (T1) 1 year post surgery (T2)

GBP GB GBP GB

GLP-1

 Fasting ↔ ↔ ↔ ↔

 3 h AUC ↑ ↔ ↑ ↔

PYY

 Fasting ↔ ↔ ↔ ↔

 3 h AUC ↑ ↔ ↑ ↔

Ghrelin

 Fasting ↔ ↔ ↔ ↔

 3 h AUC ↔ ↔ ↑ ↔

Amylin

 Fasting ↓ ↔ ↓ ↔

 3 h AUC ↓ ↔ ↓ ↔

Fasting Leptin ↓ ↓↔ ↓ ↓↔

aSummary of effects from baseline. Bold arrows indicate statistically significant changes from baseline.

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