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The Effects of Calorie Restriction and Bariatric Surgery on Circulating Proneurotensin Levels

Miskelly, Michael G. LU ; Berggren, Johan LU ; Svensson, Malin LU ; Koffert, Jukka ; Honka, Henri ; Kauhanen, Saila ; Nuutila, Pirjo ; Hedenbro, Jan LU ; Lindqvist, Andreas LU and Melander, Olle LU orcid , et al. (2025) In Journal of Clinical Endocrinology and Metabolism 110(2). p.497-505
Abstract

Context: Proneurotensin (pNT) is associated with obesity and type 2 diabetes (T2D), but the effects of Roux-en-Y gastric bypass (RYGB) on postprandial pNT levels are not well studied. Objective: This work aimed to assess the effects of RYGB vs a very low-energy diet (VLED) on pNT levels in response to mixed-meal tests (MMTs), and long-term effects of RYGB on fasting pNT. Methods: Cohort 1: Nine normoglycemic (NG) and 10 T2D patients underwent MMT before and after VLED, immediately post RYGB and 6 weeks post RYGB. Cohort 2: Ten controls with normal weight and 10 patients with obesity and T2D, who underwent RYGB or vertical sleeve gastrectomy (VSG), underwent MMTs and glucose-dependent insulinotropic polypeptide (GIP) infusions pre... (More)

Context: Proneurotensin (pNT) is associated with obesity and type 2 diabetes (T2D), but the effects of Roux-en-Y gastric bypass (RYGB) on postprandial pNT levels are not well studied. Objective: This work aimed to assess the effects of RYGB vs a very low-energy diet (VLED) on pNT levels in response to mixed-meal tests (MMTs), and long-term effects of RYGB on fasting pNT. Methods: Cohort 1: Nine normoglycemic (NG) and 10 T2D patients underwent MMT before and after VLED, immediately post RYGB and 6 weeks post RYGB. Cohort 2: Ten controls with normal weight and 10 patients with obesity and T2D, who underwent RYGB or vertical sleeve gastrectomy (VSG), underwent MMTs and glucose-dependent insulinotropic polypeptide (GIP) infusions pre surgery and 3 months post surgery. Glucagon-like peptide-1 (GLP-1) infusions were performed in normal-weight participants. Cohort 3: Fasting pNT was assessed pre RYGB (n = 161), 2 months post RYGB (n = 92), and 1year post RYGB (n = 118) in NG and T2D patients. pNT levels were measured using enzyme-linked immunosorbent assay. Results: Reduced fasting and postprandial pNT were evident after VLED and immediately following RYGB. Reintroduction of solid food post RYGB increased fasting and postprandial pNT. Prior to RYGB, all patients lacked a meal response in pNT, but this was evident post RYGB/VSG. GIP or GLP-1 infusion had no effect on pNT levels. Fasting pNTs were higher 1-year post RYGB regardless of glycemic status. Conclusion: RYGB causes a transient reduction in pNT as a consequence of caloric restriction. The RYGB/VSG-induced rise in postprandial pNT is independent of GIP and GLP-1, and higher fasting pNTs are maintained 1 year post surgically.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
calorie restriction, gastric bypass, pNT, RYGB
in
Journal of Clinical Endocrinology and Metabolism
volume
110
issue
2
pages
497 - 505
publisher
Oxford University Press
external identifiers
  • pmid:38477483
  • scopus:85216606761
ISSN
0021-972X
DOI
10.1210/clinem/dgae147
language
English
LU publication?
yes
additional info
Publisher Copyright: © The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved.
id
36305201-8461-434e-84b2-05673ae00619
date added to LUP
2025-03-27 15:59:30
date last changed
2025-07-17 23:51:30
@article{36305201-8461-434e-84b2-05673ae00619,
  abstract     = {{<p>Context: Proneurotensin (pNT) is associated with obesity and type 2 diabetes (T2D), but the effects of Roux-en-Y gastric bypass (RYGB) on postprandial pNT levels are not well studied. Objective: This work aimed to assess the effects of RYGB vs a very low-energy diet (VLED) on pNT levels in response to mixed-meal tests (MMTs), and long-term effects of RYGB on fasting pNT. Methods: Cohort 1: Nine normoglycemic (NG) and 10 T2D patients underwent MMT before and after VLED, immediately post RYGB and 6 weeks post RYGB. Cohort 2: Ten controls with normal weight and 10 patients with obesity and T2D, who underwent RYGB or vertical sleeve gastrectomy (VSG), underwent MMTs and glucose-dependent insulinotropic polypeptide (GIP) infusions pre surgery and 3 months post surgery. Glucagon-like peptide-1 (GLP-1) infusions were performed in normal-weight participants. Cohort 3: Fasting pNT was assessed pre RYGB (n = 161), 2 months post RYGB (n = 92), and 1year post RYGB (n = 118) in NG and T2D patients. pNT levels were measured using enzyme-linked immunosorbent assay. Results: Reduced fasting and postprandial pNT were evident after VLED and immediately following RYGB. Reintroduction of solid food post RYGB increased fasting and postprandial pNT. Prior to RYGB, all patients lacked a meal response in pNT, but this was evident post RYGB/VSG. GIP or GLP-1 infusion had no effect on pNT levels. Fasting pNTs were higher 1-year post RYGB regardless of glycemic status. Conclusion: RYGB causes a transient reduction in pNT as a consequence of caloric restriction. The RYGB/VSG-induced rise in postprandial pNT is independent of GIP and GLP-1, and higher fasting pNTs are maintained 1 year post surgically.</p>}},
  author       = {{Miskelly, Michael G. and Berggren, Johan and Svensson, Malin and Koffert, Jukka and Honka, Henri and Kauhanen, Saila and Nuutila, Pirjo and Hedenbro, Jan and Lindqvist, Andreas and Melander, Olle and Wierup, Nils}},
  issn         = {{0021-972X}},
  keywords     = {{calorie restriction; gastric bypass; pNT; RYGB}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{2}},
  pages        = {{497--505}},
  publisher    = {{Oxford University Press}},
  series       = {{Journal of Clinical Endocrinology and Metabolism}},
  title        = {{The Effects of Calorie Restriction and Bariatric Surgery on Circulating Proneurotensin Levels}},
  url          = {{http://dx.doi.org/10.1210/clinem/dgae147}},
  doi          = {{10.1210/clinem/dgae147}},
  volume       = {{110}},
  year         = {{2025}},
}