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

Author:

Miskelly Michael G1,Berggren Johan1,Svensson Malin2,Koffert Jukka34,Honka Henri3,Kauhanen Saila5,Nuutila Pirjo36ORCID,Hedenbro Jan1,Lindqvist Andreas1,Melander Olle2,Wierup Nils1ORCID

Affiliation:

1. Neuroendocrine Cell Biology, Lund University Diabetes Centre , Malmö 20502 , Sweden

2. Department of Clinical Sciences, Lund University , Malmö 20502 , Sweden

3. Turku PET Centre, University of Turku , Turku 20520 , Finland

4. Department of Gastroenterology, Turku University Hospital , Turku 20520,   Finland

5. Division of Digestive Surgery and Urology, Turku University Hospital , Turku 20520, Finland

6. Department of Endocrinology, Turku University Hospital , Turku 20520 , Finland

Abstract

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 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.

Funder

Swedish Research Council

Strategic Research Area Exodiab

Linnaeus

Swedish Foundation for Strategic Research

Royal Physiographic Society in Lund

The medical faculty at Lund University

Crafoord and Albert Påhlsson Foundations and from the European Research Council

Novo Nordisk Foundation

Swedish Heart and Lung Foundation

Publisher

The Endocrine Society

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