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Cited by 13Bariatric Surgery and OutcomesRegulation of Appetite and ObesityPharmacology and Obesity Treatment

Primary weight loss failure after Roux-en-Y gastric bypass is characterized by impaired gut-hormone mediated regulation of food intake

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Bojsen-Møller, Kirstine Nyvold, Svane, Maria Saur, Martinussen, Christoffer, Dirksen, Carsten, Jørgensen, Nils Bruun, Jensen, Jens-Erik Beck, Jensen, Christian Zinck, Torekov, Signe Sørensen +8 more·2023·International Journal of Obesity
DOI 10.1038/s41366-023-01372-8PMC PMC10599997
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Abstract

Background/Objectives: After Roux-en-Y gastric bypass (RYGB) a subset of patients never obtain excess BMI loss (EBMIL) > 50% and are categorized as having primary weight loss (WL) failure. We hypothesized that postprandial concentrations of glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) would be lower in patients with primary WL failure compared with patients with successfully maintained WL. Furthermore, that inhibition of gut hormone secretions would increase ad libitum food intake less in patients with primary WL failure. Subjects/Methods: Twenty women with primary WL failure (LowEBMIL < 50%) were individually matched to twenty women with successful WL (HighEBMIL > 60%) on age, preoperative BMI and time from RYGB. On separate days performed in a random order, patient-blinded subcutaneous injections of octreotide or saline (placebo) were followed by a fixed breakfast and an ad libitum lunch with blood sampling for appetite regulating hormones and Visual-Analogue-Scale (VAS)-scoring of hunger/satiety. Furthermore, participants underwent gene variant analysis for GLP-1, PYY and their receptors, indirect calorimetry, dual-energy X-ray absorptiometry (DXA)-scans, 4-days at-home food registration and 14-days step counting. Results: On placebo days, postprandial GLP-1, PYY and cholecystokinin (CCK) concentrations were similar between groups after breakfast. Fasting ghrelin was lower in LowEBMIL, but the postprandial suppression was similar. LowEBMIL had lower satiety VAS-scores and less suppression of hunger VAS-scores. Gene variants did not differ between groups. Octreotide diminished GLP-1, PYY, CCK and ghrelin concentrations in both groups. Octreotide did not affect ad libitum food intake in LowEBMIL (−1% [−13, 12], mean [95%CI]), while food intake increased in HighEBMIL (+23% [2,44]). Conclusions: Primary WL failure after RYGB was not characterized by impaired secretions of appetite regulating gut hormones. Interestingly, inhibition of gut hormone secretions with octreotide only increased food intake in patients with successful WL post-RYGB. Thus, an impaired central anorectic response to gut hormones may contribute to primary WL failure after RYGB.

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  • To date, the majority of the literature on weight regain physiology is based on dietary or surgically induced weight loss.

    “To date, the majority of the literature on weight regain physiology is based on dietary or surgically induced weight loss.”

    From The societal implications of using glucagon-like peptide-1 receptor agonists for the treatment of obesity (2025) · cites this paper as [83]

    The Introduction (page unavailable) discusses prior studies of gut hormones and weight regain after Roux-en-Y gastric bypass, supporting the surgical-weight-loss part. It does not assess the weight-regain physiology literature as a whole or establish that most of it concerns dietary or surgically induced weight loss; a search for diet-induced weight loss did not find that comparison. (LLM, conf=0.76)

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Cited by

Sorted by citations

Authors
Bojsen-Møller, K. N., Svane, M. S., Martinussen, C., Dirksen, C., Jørgensen, N. B., Jensen, J.-E. B., Jensen, C. Z., Torekov, S. S., Kristiansen, V. B., Rehfeld, J. F., Bork-Jensen, J., Grarup, N., Hansen, T., Hartmann, B., Holst, J. J., & Madsbad, S.
Affiliations
  • University of Copenhagen (DK)
  • Hvidovre Hospital (DK)
  • Rigshospitalet (DK)
Corresponding author
Bojsen-Møller, Kirstine Nyvold
ORCID
Venue
International Journal of Obesity
Publisher
Springer Science and Business Media LLC
Published
2023-08-31
Volume
47
Issue
11
Pages
1143-1151
ISSN
  • 0307-0565 (ISSN-L)
  • 1476-5497
DOI
10.1038/s41366-023-01372-8
PMC
PMC10599997
OpenAlex
W4386329860
Cited by
13
References
3
Citations by year
2026: 3 · 2025: 4 · 2024: 6
FWCI
3.48
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Obesity (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
Funders
  • European Commission (HORIZON2020)
  • Gentofte Hospital
  • Novo Nordisk
  • Danmarks Frie Forskningsfond
  • Novo Nordisk Fonden (NNF23OC0084305, NNF20SA0064144, NNF16OC0019968, NNF15OC0016692, NNF18 OC0032330)
  • H2020 European Research Council (695069)
Topics
  • Health Sciences › Medicine › Surgery › Bariatric Surgery and Outcomes
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
Keywords
Roux-en-Y gastric bypass, excess BMI loss, gastrointestinal hormones, food intake regulation, octreotide, glucagon-like peptide-1, peptide YY, cholecystokinin, ghrelin, satiety, hunger, appetite regulation, bariatric surgery outcomes, women, genetic variants
MeSH terms
Cholecystokinin, Eating, Female, Gastrointestinal Hormones, Humans, Octreotide, Gastric Bypass, Weight Loss, Peptide YY, Glucagon-Like Peptide 1, Ghrelin

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