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Gastric Bypass in Morbid Obesity: Postoperative Changes in Metabolic, Inflammatory and Gut Regulatory Peptides
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis examines the effect of surgical weight loss on gut and adipose tissue peptides involved in appetite regulation and energy homeostasis in morbidly obese humans. Roux-en-Y gastric bypass (RYGBP) is the gold standard operation used for effective long-term weight loss and improved health. The exact mechanisms for this outcome are under investigation.

We measured ghrelin, a recently discovered hunger hormone, insulin, adiponectin and leptin along with anthropometry measures in 66 morbidly obese patients prior to and 6 and 12 months after RYGBP. Impressive weight loss occurred postoperatively as did alterations in the peptides. Consistent correlations were found between weight, leptin, ghrelin and insulin. The main findings were low ghrelin concentrations in obesity and an increase after RYGBP.

We explored inflammatory proteins C-reactive protein (CRP), serum amyloid A and interleukin-6 before and during massive weight loss 6 and 12 months after RYGBP in morbidly obese subjects. The studied proteins declined after surgery and a correlation between CRP and homeostatic model of assessment for insulin resistance, independent of BMI, strongly linked insulin resistance and inflammation. CRP declined most in insulin-sensitive subjects.

We examined the excluded stomach mucosa and vagus nerve by measuring gastrin, pepsinogen I (PGI), pancreatic polypeptide (PP) and ghrelin levels during week 1 and year after RYGBP. Ghrelin levels rose with weight loss but declined 24-hours after surgery, like PP, indicating transient vagal nerve damage. Low levels of gastrin and PGI suggest a resting mucosa.

We evaluated gut peptides: peptide YY (PYY), glucaogon like peptide-1 (GLP-1), pro-neurotensin (pro-NT) and PP, in lean (young and middle-aged), obese and postoperative RYGBP subjects pre- and postprandially. RYGBP subjects had exaggerated levels of PYY and GLP-1 postprandially and higher basal proNT levels, implying a ‘satiety peptide tone’ that may contribute to the maintenance of weight loss.

In summary, RYGBP results in marked weight loss and alterations in gut and adipose tissue peptides involved in appetite regulation and energy homeostasis. These postoperative peptide changes may contribute to impressive weight loss observed after RYGBP.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2008. , 59 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 380
Keyword [en]
gastric bypass, morbid obesity, ghrelin, C-reactive protein, pancreatic polypeptide, peptide YY, glucagon-like peptide-1
National Category
Clinical Science
Identifiers
URN: urn:nbn:se:uu:diva-9297ISBN: 978-91-554-7293-1 (print)OAI: oai:DiVA.org:uu-9297DiVA: diva2:172583
Public defence
2008-10-25, Enghoffsalen, Entrance 50, University Hospital Uppsala, 09:15
Opponent
Supervisors
Available from: 2008-10-02 Created: 2008-10-02Bibliographically approved
List of papers
1. Ghrelin and Adipose Tissue Regulatory Peptides: Effect of Gastric Bypass Surgery in Obese Humans
Open this publication in new window or tab >>Ghrelin and Adipose Tissue Regulatory Peptides: Effect of Gastric Bypass Surgery in Obese Humans
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2003 In: The Journal of Clinical Endocrinology & Metabolism, ISSN 0021-972X, Vol. 88, no 7, 3177-3183 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-97580 (URN)
Available from: 2008-10-02 Created: 2008-10-02Bibliographically approved
2. CRP reduction following gastric bypass surgery is most
Open this publication in new window or tab >>CRP reduction following gastric bypass surgery is most
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2005 In: International Journal of Obesity, ISSN 0307-0565, Vol. 29, no 10, 1275- p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-97581 (URN)
Available from: 2008-10-02 Created: 2008-10-02Bibliographically approved
3. Early Changes in Ghrelin following Roux-en-Y Gastric Bypass: Influence of Vagal Nerve Functionality?
Open this publication in new window or tab >>Early Changes in Ghrelin following Roux-en-Y Gastric Bypass: Influence of Vagal Nerve Functionality?
2007 (English)In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 17, no 3, 304-310 p.Article in journal (Refereed) Published
Abstract [en]

Background  Roux-en-Y gastric bypass (RYGBP) effectively produces massive weight reduction, improving health in morbidly obese patients. The mechanisms for the weight loss, and the fate of the excluded gastric mucosa, are not fully clarified. To what extent the appetite-stimulating gastric peptide ghrelin is affected remains controversial. Methods  Circulating concentrations of ghrelin, pancreatic polypeptide (PP), pepsinogen I (PGI) and gastrin were examined in 15 morbidly obese patients (median BMI 45 kg/m2) preoperatively, and on days 1, 2, 4, 6 and at months 1, 6 and 12 after RYGBP. Results  Ghrelin levels fell on postoperative day 1 and increased after 1 month to preoperative levels, and rose further at 6 and 12 months. PP concentrations decreased on day 1 and subsequently returned to preoperative levels. PGI levels peaked transiently the first days after surgery and subsequently declined to lower than preoperative levels. Gastrin levels were gradually reduced postoperatively. Conclusion  Ghrelin and PP fall transiently after surgery, possibly due to vagal dysfunction, and ultimately, as weight loss ensues, ghrelin secretion increases to higher than preoperative levels. The RYBGP procedure affects the gastric mucosa, as reflected by a transient increase in circulating PGI, and subsequently, the mucosa in the excluded stomach is at rest, as shown by low levels of PGI and gastrin.

Keyword
gastric bypass, ghrelin, pepsinogen, gastrin, pancreatic polypeptide, morbid obesity, vagus nerve
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-97582 (URN)10.1007/s11695-007-9056-8 (DOI)000245043900004 ()17546836 (PubMedID)
Available from: 2008-10-02 Created: 2008-10-02 Last updated: 2017-12-14Bibliographically approved
4. Postprandial changes in gut regulatory peptides in gastric bypass patients
Open this publication in new window or tab >>Postprandial changes in gut regulatory peptides in gastric bypass patients
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2008 (English)In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 32, 1640-6 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: The marked weight loss induced by Roux-en-Y gastric bypass (RYGBP) for morbid obesity is still incompletely understood. It has been suggested that, besides the restriction imposed by the surgical procedure, alterations in gut regulatory peptides signaling the brain might contribute. The aim of this study was to measure the putative satiety peptides peptide YY (PYY), glucagon-like peptide-1 (GLP-1), pancreatic polypeptide (PP) and pro-neurotensin (pro-NT) in response to fasting and feeding. DESIGN: The study is a cross-sectional study. After a prolonged overnight 14 h fast, a standardized mixed meal (574 kcal) was provided. Blood samples for peptide measurements were obtained before and after the meal. SUBJECTS: Forty subjects (20 males and females) were included; 10 morbidly obese; (mean age 41+/-7 years; mean BMI 44+/-3 kg/m(2)), 10 operated with RYGBP (age 45+/-5 years; BMI 35+/-6 kg/m(2)), 10 aged-matched lean (age 44+/-5 years; BMI 24+/-3 kg/m(2)) and 10 young lean subjects (age 26+/-2 years; BMI 23+/-2 kg/m(2)). MEASUREMENTS: Plasma concentrations of PYY, GLP-1, PP and pro-NT were obtained. RESULTS: PYY levels increased more in the RYGBP group than in the other groups after the test meal. GLP-1 levels rose in the RYGBP patients, with a small increase seen in the age-matched lean group. PP concentrations increased similarly in all groups postprandially. Pro-NT levels were highest in surgical patients, with no meal effect. CONCLUSION: RYGBP subjects displayed exaggerated PYY and GLP-1 responses to a standardized meal and demonstrated higher pro-NT levels both pre- and postprandially. The findings indicate that possibly the alterations in gut peptide secretion may promote weight loss after gastric bypass surgery.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-97583 (URN)10.1038/ijo.2008.157 (DOI)000260925300006 ()18794895 (PubMedID)
Available from: 2008-10-02 Created: 2008-10-02 Last updated: 2017-12-14Bibliographically approved

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