Background: Roux-en-Y gastric bypass (RYGB) imparts long-term weight loss, the mechanisms for which are not well understood. Changes in leptin and gastrointestinal (GI) hormones, including glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and ghrelin, may contribute to the relative success of RYGB compared with conventional weight loss methods. This study evaluated changes in GI hormones and leptin post-RYGB. The study also evaluated whether GI hormones differed after a short-term dose of protein or fat. Methods: GLP-1, PYY, ghrelin, and leptin were assessed in 16 women before RYGB and up to 1 year after RYGB. Plasma was collected before and at several times after a short-term equicaloric dose of protein or fat. Results: GLP-1 area under the curve (AUC) increased at week 6 and 1 year in the fat beverage (FAT-BEV) group compared with baseline. PYY AUC remained elevated at 1 year in the FAT-BEV group. Ghrelin AUC decreased at week 2, week 6, and 1 year in the protein beverage (PRO-BEV) group compared with baseline. Ghrelin AUC was lower in the PRO-BEV group compared with the FAT-BEV group at week 6. Fasted leptin decreased at all visits in both groups and was lower in the FAT-BEV group compared with the PRO-BEV group at 1 year. Conclusions: Changes from baseline were evident for all GI hormones and leptin; some differences were evident soon after surgery (ghrelin, leptin), whereas others were maintained long term (GLP-1, PYY, ghrelin, leptin). In response to a short-term stimulus, protein suppressed ghrelin and fat potently stimulated GLP-1 and PYY. Future work in this area is warranted.
BrolinRE. Bariatric surgery and long-term control of morbid obesity. JAMA. 2002;288:2793-2796.
2.
SmithBRSchauerPNguyenNT. Surgical approaches to the treatment of obesity: bariatric surgery. Endocrinol Metab Clin North Am. 2008;37:943-964.
3.
SalibaJWattacherilJAbumradNN. Endocrine and metabolic response to gastric bypass. Curr Opin Clin Nutr Metab Care. 2009;12:515-521.
4.
BuchwaldH; Consensus Conference Panel. Consensus conference statement bariatric surgery for morbid obesity: health implications for patients, health professionals, and third-party payers. Surg Obes Relat Dis. 2005;1:371-381.
5.
ElderKAWolfeBM. Bariatric surgery: a review of procedures and outcomes. Gastroenterology. 2007;132:2253-2271.
6.
PilkingtonTRGazetJCAngLKalucyRSCrispAHDayS. Explanations for weight loss after ileojejunal bypass in gross obesity. Br Med J. 1976;1:1504-1505.
7.
KornerJInabnetWFebresG. Prospective study of gut hormone and metabolic changes after adjustable gastric banding and Roux-en-Y gastric bypass. Int J Obes (Lond). 2009;33:786-795.
8.
TohSYZarshenasNJorgensenJ. Prevalence of nutrient deficiencies in bariatric patients. Nutrition. 2009;25:1150-1156.
9.
BorgCMle RouxCWGhateiMABloomSRPatelAGAylwinSJ. Progressive rise in gut hormone levels after Roux-en-Y gastric bypass suggests gut adaptation and explains altered satiety. Br J Surg. 2006;93:210-215.
10.
HoldstockCZetheliusBSundbomMKarlssonFAEdén EngströmB. Postprandial changes in gut regulatory peptides in gastric bypass patients. Int J Obes (Lond). 2008;32:1640-1646.
11.
le RouxCWAylwinSJBatterhamRL. Gut hormone profiles following bariatric surgery favor an anorectic state, facilitate weight loss, and improve metabolic parameters. Ann Surg. 2006;243:108-114.
12.
BaggioLLDruckerDJ. Biology of incretins: GLP-1 and GIP. Gastroenterology. 2007;132:2131-2157.
13.
CummingsDEOverduinJ. Gastrointestinal regulation of food intake. J Clin Invest. 2007;117:13-23.
14.
MurphyKGBloomSR. Gut hormones and the regulation of energy homeostasis. Nature. 2006;444:854-859.
15.
WrenAMBloomSR. Gut hormones and appetite control. Gastroenterology. 2007;132:2116-2130.
16.
VincentRPle RouxCW. Changes in gut hormones after bariatric surgery. Clin Endocrinol (Oxf). 2008;69:173-179.
17.
DhilloWS. Appetite regulation: an overview. Thyroid. 2007;17:433-445.
18.
DubePEBrubakerPL. Nutrient, neural and endocrine control of glucagon-like peptide secretion. Horm Metab Res. 2004;36:755-760.
19.
FrezzaEEWachtelMSChiriva-InternatiM. The multiple faces of glucagon-like peptide-1–obesity, appetite, and stress: what is next? A review. Dig Dis Sci. 2007;52:643-649.
20.
le RouxCWBloomSR. Peptide YY, appetite and food intake. Proc Nutr Soc. 2005;64:213-216.
21.
VincentRPAshrafianHle RouxCW. Mechanisms of disease: the role of gastrointestinal hormones in appetite and obesity. Nat Clin Pract Gastroenterol Hepatol. 2008;5:268-277.
22.
JayasenaCNBloomSR. Role of gut hormones in obesity. Endocrinol Metab Clin North Am. 2008;37:769-787, xi.
23.
Van CittersGWLinHC. The ileal brake: a fifteen-year progress report. Curr Gastroenterol Rep. 1999;1:404-409.
24.
CoppiniLZWaitzbergDLCamposAC. Limitations and validation of bioelectrical impedance analysis in morbidly obese patients. Curr Opin Clin Nutr Metab Care. 2005;8:329-332.
25.
DeaconCF. What do we know about the secretion and degradation of incretin hormones?Regul Pept. 2005;128:117-124.
26.
AdrianTEFerriGLBacarese-HamiltonAJFuesslHSPolakJMBloomSR. Human distribution and release of a putative new gut hormone, peptide YY. Gastroenterology. 1985;89:1070-1077.
27.
YoderSMYangQKindelTLTsoP. Stimulation of incretin secretion by dietary lipid: is it dose dependent?Am J Physiol Gastrointest Liver Physiol. 2009;297:G299-G305.
28.
HerrmannCGokeRRichterGFehmannHCArnoldRGokeB. Glucagon-like peptide-1 and glucose-dependent insulin-releasing polypeptide plasma levels in response to nutrients. Digestion. 1995;56:117-126.
29.
MaffeisCSuranoMGCordioliSGasperottiSCorradiMPinelliL. A high-fat vs a moderate-fat meal in obese boys: nutrient balance, appetite, and gastrointestinal hormone changes. Obesity (Silver Spring). 2010;18:449-455.
30.
BowenJNoakesMCliftonPM. Appetite regulatory hormone responses to various dietary proteins differ by body mass index status despite similar reductions in ad libitum energy intake. J Clin Endocrinol Metab. 2006;91:2913-2919.
31.
BowenJNoakesMCliftonPM. Appetite hormones and energy intake in obese men after consumption of fructose, glucose and whey protein beverages. Int J Obes (Lond). 2007;31:1696-1703.
32.
EssahPALevyJRSistrunSNKellySMNestlerJE. Effect of macronutrient composition on postprandial peptide YY levels. J Clin Endocrinol Metab. 2007;92:4052-4055.
33.
MaljaarsJRomeynEAHaddemanEPetersHPMascleeAA. Effect of fat saturation on satiety, hormone release, and food intake. Am J Clin Nutr. 2009;89:1019-1024.
34.
SeimonRVFeltrinKLMeyerJH. Effects of varying combinations of intraduodenal lipid and carbohydrate on antropyloroduodenal motility, hormone release, and appetite in healthy males. Am J Physiol Regul Integr Comp Physiol. 2009;296:R912-R920.
35.
HelouNObeidOAzarSTHwallaN. Variation of postprandial PYY 3-36 response following ingestion of differing macronutrient meals in obese females. Ann Nutr Metab. 2008;52:188-195.
36.
BatterhamRLHeffronHKapoorS. Critical role for peptide YY in protein-mediated satiation and body-weight regulation. Cell Metab. 2006;4:223-233.
37.
VerdichCToubroSBuemannBLysgård MadsenJJuul HolstJAstrupA. The role of postprandial releases of insulin and incretin hormones in meal-induced satiety—effect of obesity and weight reduction. Int J Obes Relat Metab Disord. 2001;25:1206-1214.
38.
BatterhamRLCohenMAEllisSM. Inhibition of food intake in obese subjects by peptide YY3-36. N Engl J Med. 2003;349:941-948.
39.
le RouxCWBatterhamRLAylwinSJ. Attenuated peptide YY release in obese subjects is associated with reduced satiety. Endocrinology. 2006;147:3-8.
40.
Alvarez BartolomeMBorqueMMartinez-SarmientoJ. Peptide YY secretion in morbidly obese patients before and after vertical banded gastroplasty. Obes Surg. 2002;12:324-327.
41.
le RouxCWWelbournRWerlingM. Gut hormones as mediators of appetite and weight loss after Roux-en-Y gastric bypass. Ann Surg. 2007;246:780-785.
42.
MorinigoRLacyAMCasamitjanaRDelgadoSGomisRVidalJ. GLP-1 and changes in glucose tolerance following gastric bypass surgery in morbidly obese subjects. Obes Surg. 2006;16:1594-1601.
43.
WhitsonBALeslieDBKelloggTA. Entero-endocrine changes after gastric bypass in diabetic and nondiabetic patients: a preliminary study. J Surg Res. 2007;141:31-39.
44.
KornerJBesslerMCiriloLJ. Effects of Roux-en-Y gastric bypass surgery on fasting and postprandial concentrations of plasma ghrelin, peptide YY, and insulin. J Clin Endocrinol Metab. 2005;90:359-365.
45.
ChanJLMunECStoynevaVMantzorosCSGoldfineAB. Peptide YY levels are elevated after gastric bypass surgery. Obesity (Silver Spring). 2006;14:194-198.
46.
KornerJInabnetWConwellIM. Differential effects of gastric bypass and banding on circulating gut hormone and leptin levels. Obesity (Silver Spring). 2006;14:1553-1561.
47.
MorinigoRVidalJLacyAMDelgadoSCasamitjanaRGomisR. Circulating peptide YY, weight loss, and glucose homeostasis after gastric bypass surgery in morbidly obese subjects. Ann Surg. 2008;247:270-275.
48.
RodieuxFGiustiVD’AlessioDASuterMTappyL. Effects of gastric bypass and gastric banding on glucose kinetics and gut hormone release. Obesity (Silver Spring). 2008;16:298-305.
49.
GoldfineABMunECDevineE. Patients with neuroglycopenia after gastric bypass surgery have exaggerated incretin and insulin secretory responses to a mixed meal. J Clin Endocrinol Metab. 2007;92:4678-4685.
50.
KornerJBesslerMInabnetWTaverasCHolstJJ. Exaggerated glucagon-like peptide-1 and blunted glucose-dependent insulinotropic peptide secretion are associated with Roux-en-Y gastric bypass but not adjustable gastric banding. Surg Obes Relat Dis. 2007;3:597-601.
51.
MorínigoRMoizéVMusriM. Glucagon-like peptide-1, peptide YY, hunger, and satiety after gastric bypass surgery in morbidly obese subjects. J Clin Endocrinol Metab. 2006;91:1735-1740.
52.
Zwirska-KorczalaKKonturekSJSodowskiM. Basal and postprandial plasma levels of PYY, ghrelin, cholecystokinin, gastrin and insulin in women with moderate and morbid obesity and metabolic syndrome. J Physiol Pharmacol. 2007;58(suppl 1):13-35.
53.
CummingsDEPurnellJQFrayoRSSchmidovaKWisseBEWeigleDS. A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes. 2001;50:1714-1719.
54.
ErdmannJLipplFSchusdziarraV. Differential effect of protein and fat on plasma ghrelin levels in man. Regul Pept. 2003;116:101-107.
55.
Tannous dit El KhouryDObeidOAzarSTHwallaN. Variations in postprandial ghrelin status following ingestion of high-carbohydrate, high-fat, and high-protein meals in males. Ann Nutr Metab. 2006;50:260-269.
56.
BowenJNoakesMTrenerryCCliftonPM. Energy intake, ghrelin, and cholecystokinin after different carbohydrate and protein preloads in overweight men. J Clin Endocrinol Metab. 2006;91:1477-1483.
57.
Foster-SchubertKEOverduinJPrudomCE. Acyl and total ghrelin are suppressed strongly by ingested proteins, weakly by lipids, and biphasically by carbohydrates. J Clin Endocrinol Metab. 2008;93:1971-1979.
58.
BlomWALluchAStafleuA. Effect of a high-protein breakfast on the postprandial ghrelin response. Am J Clin Nutr. 2006;83:211-220.
59.
CummingsDEWeigleDSFrayoRS. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med. 2002;346:1623-1630.
60.
CouceMECottamDEsplenJSchauerPBurgueraB. Is ghrelin the culprit for weight loss after gastric bypass surgery? A negative answer. Obes Surg. 2006;16:870-878.
61.
TritosNAMunEBertkauAGraysonRMaratos-FlierEGoldfineA. Serum ghrelin levels in response to glucose load in obese subjects post-gastric bypass surgery. Obes Res. 2003;11:919-924.
62.
LinEGletsuNFugateK. The effects of gastric surgery on systemic ghrelin levels in the morbidly obese. Arch Surg. 2004;139:780-784.
63.
MorínigoRCasamitjanaRMoizéV. Short-term effects of gastric bypass surgery on circulating ghrelin levels. Obes Res. 2004;12:1108-1116.
64.
ChristouNVLookDMcLeanAP. Pre- and post-prandial plasma ghrelin levels do not correlate with satiety or failure to achieve a successful outcome after Roux-en-Y gastric bypass. Obes Surg. 2005;15:1017-1023.
65.
LeonettiFSilecchiaGIacobellisG. Different plasma ghrelin levels after laparoscopic gastric bypass and adjustable gastric banding in morbid obese subjects. J Clin Endocrinol Metab. 2003;88:4227-4231.
66.
EngstromBEOhrvallMSundbomMLindLKarlssonFA. Meal suppression of circulating ghrelin is normalized in obese individuals following gastric bypass surgery. Int J Obes (Lond). 2007;31:476-480.
67.
FarajMHavelPJPhelisSBlankDSnidermanADCianfloneK. Plasma acylation-stimulating protein, adiponectin, leptin, and ghrelin before and after weight loss induced by gastric bypass surgery in morbidly obese subjects. J Clin Endocrinol Metab. 2003;88:1594-1602.
68.
HoldstockCEngstromBEOhrvallMLindLSundbomMKarlssonFA. Ghrelin and adipose tissue regulatory peptides: effect of gastric bypass surgery in obese humans. J Clin Endocrinol Metab. 2003;88:3177-3183.
69.
SundbomMHoldstockCEngstromBEKarlssonFA. Early changes in ghrelin following Roux-en-Y gastric bypass: influence of vagal nerve functionality?Obes Surg. 2007;17:304-310.
70.
StoeckliRChandaRLangerIKellerU. Changes of body weight and plasma ghrelin levels after gastric banding and gastric bypass. Obes Res. 2004;12:346-350.
71.
KaramanakosSNVagenasKKalfarentzosFAlexandridesTK. Weight loss, appetite suppression, and changes in fasting and postprandial ghrelin and peptide-YY levels after Roux-en-Y gastric bypass and sleeve gastrectomy: a prospective, double blind study. Ann Surg. 2008;247:401-407.
72.
ManciniMCCostaAPde MeloME. Effect of gastric bypass on spontaneous growth hormone and ghrelin release profiles. Obesity (Silver Spring). 2006;14:383-387.
73.
VendrellJBrochMVilarrasaN. Resistin, adiponectin, ghrelin, leptin, and proinflammatory cytokines: relationships in obesity. Obes Res. 2004;12:962-971.
74.
FriedmanJM. Obesity in the new millennium. Nature. 2000;404:632-634.
BloomgardenZT. Gut and adipocyte peptides. Diabetes Care. 2006;29:450-456.
77.
Konopko-ZubrzyckaMBaniukiewiczAWroblewskiE. The effect of intragastric balloon on plasma ghrelin, leptin, and adiponectin levels in patients with morbid obesity. J Clin Endocrinol Metab. 2009;94:1644-1649.
78.
OlivanBTeixeiraJBoseM. Effect of weight loss by diet or gastric bypass surgery on peptide YY3-36 levels. Ann Surg. 2009;249:948-953.
79.
RatliffJMutungiGPuglisiMJVolekJSFernandezML. Carbohydrate restriction (with or without additional dietary cholesterol provided by eggs) reduces insulin resistance and plasma leptin without modifying appetite hormones in adult men. Nutr Res. 2009;29:262-268.
80.
WeigleDSBreenPAMatthysCC. A high-protein diet induces sustained reductions in appetite, ad libitum caloric intake, and body weight despite compensatory changes in diurnal plasma leptin and ghrelin concentrations. Am J Clin Nutr. 2005;82:41-48.
81.
CzupryniakLPawlowskiMKumorASzymanskiDLobaJStrzelczykJ. Predicting maximum Roux-en-Y gastric bypass-induced weight reduction—preoperative plasma leptin or body weight?Obes Surg. 2007;17:162-167.
82.
FruhbeckGDiez-CaballeroAGilMJ. The decrease in plasma ghrelin concentrations following bariatric surgery depends on the functional integrity of the fundus. Obes Surg. 2004;14:606-612.
83.
MolinaAVendrellJGutierrezC. Insulin resistance, leptin and TNF-alpha system in morbidly obese women after gastric bypass. Obes Surg. 2003;13:615-621.
84.
RamosAPde AbreuMRVendraminiRCBrunettiILPepatoMT. Decrease in circulating glucose, insulin and leptin levels and improvement in insulin resistance at 1 and 3 months after gastric bypass. Obes Surg. 2006;16:1359-1364.
85.
RubinoFGagnerMGentileschiP. The early effect of the Roux-en-Y gastric bypass on hormones involved in body weight regulation and glucose metabolism. Ann Surg. 2004;240:236-242.
86.
SwarbrickMMStanhopeKLAustrheim-SmithIT. Longitudinal changes in pancreatic and adipocyte hormones following Roux-en-Y gastric bypass surgery. Diabetologia. 2008;51:1901-1911.
87.
DasSKRobertsSBMcCroryMA. Long-term changes in energy expenditure and body composition after massive weight loss induced by gastric bypass surgery. Am J Clin Nutr. 2003;78:22-30.
88.
WhitsonBALeslieDBKelloggTA. Adipokine response in diabetics and nondiabetics following the Roux-en-Y gastric bypass: a preliminary study. J Surg Res. 2007;142:295-300.
89.
Bobbioni-HarschEMorelPHuberO. Energy economy hampers body weight loss after gastric bypass. J Clin Endocrinol Metab. 2000;85:4695-4700.
90.
RiedlMVilaGMaierC. Plasma osteopontin increases after bariatric surgery and correlates with markers of bone turnover but not with insulin resistance. J Clin Endocrinol Metab. 2008;93:2307-2312.
91.
MeierCABobbioniEGabayCAssimacopoulos-JeannetFGolayADayerJM. IL-1 receptor antagonist serum levels are increased in human obesity: a possible link to the resistance to leptin?J Clin Endocrinol Metab. 2002;87:1184-1188.
HickeyMSPoriesWJMacDonaldKGJr. A new paradigm for type 2 diabetes mellitus: could it be a disease of the foregut?Ann Surg. 1998;227:637-644.
94.
SavageAPAdrianTECarolanGChatterjeeVKBloomSR. Effects of peptide YY (PYY) on mouth to caecum intestinal transit time and on the rate of gastric emptying in healthy volunteers. Gut. 1987;28:166-170.
95.
KreymannBWilliamsGGhateiMABloomSR. Glucagon-like peptide-1 7-36: a physiological incretin in man. Lancet. 1987;2:1300-1304.
96.
AdrianTEBloomSRBryantMGPolakJMHeitzPHBarnesAJ. Distribution and release of human pancreatic polypeptide. Gut. 1976;17:940-944.
97.
PattersonMMurphyKGle RouxCWGhateiMABloomSR. Characterization of ghrelin-like immunoreactivity in human plasma. J Clin Endocrinol Metab. 2005;90:2205-2211.
98.
Westerterp-PlantengaMSLuscombe-MarshNLejeuneMPGM. Dietary protein, metabolism, and body-weight regulation: dose-response effects. Int J Obes. 2006;30:S16-S23.
99.
SoenenSWesterterp-PlantengaMS. Proteins and satiety: implications for weight management. Curr Opin Clin Nutr Metab Care. 2008;11:747-751.
100.
LaferrereBTeixeiraJMcGintyJ. Effect of weight loss by gastric bypass surgery versus hypocaloric diet on glucose and incretin levels in patients with type 2 diabetes. J Clin Endocrinol Metab. 2008;93:2479-2485.
101.
LaferrereBHeshkaSWangK. Incretin levels and effect are markedly enhanced 1 month after Roux-en-Y gastric bypass surgery in obese patients with type 2 diabetes. Diabetes Care. 2007;30:1709-1716.
102.
ClementsRHGonzalezQHLongCIWittertGLawsHL. Hormonal changes after Roux-en Y gastric bypass for morbid obesity and the control of type-II diabetes mellitus. Am Surg. 2004;70:1-5.
103.
NäslundEKralJ. Impact of gastric bypass surgery on gut hormones and glucose homeostasis in type 2 diabetes. Diabetes. 2006;55(suppl 2):S92-S97.
104.
CummingsDEOverduinJFoster-SchubertKE. Gastric bypass for obesity: mechanisms of weight loss and diabetes resolution. J Clin Endocrinol Metab. 2004;89:2608-2615.
105.
VidalJNicolauJRomeroF. Long-term effects of Roux-en-Y gastric bypass surgery on plasma glucagon-like peptide-1 and islet function in morbidly obese subjects. J Clin Endocrinol Metab. 2009;94:884-891.
106.
Van CittersGWLinHC. Ileal brake: neuropeptidergic control of intestinal transit. Curr Gastroenterol Rep. 2006;8:367-373.
107.
PournarasDJOsborneAHawkinsSC. The gut hormone response following Roux-en-Y gastric bypass: cross-sectional and prospective study. Obes Surg. 2009;20:56-60.
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