Gut Mucosal Gene Expression and Metabolic Changes After Roux-en-Y Gastric Bypass Surgery

Tina Jorsal; Marie M Christensen; Brynjulf Mortensen; Eva B Nygaard; Chen Zhang; Kristoffer Rigbolt; Erik Wandall; Ebbe Langholz; Steffen Friis; Dorte Worm; Andrea Floyd; Frederik Helgstrand; René K Støving; Alin R Aldries; Claus B Juhl; Torben Østergaard; Thomas Rydborg; Julie L Forman; Frederik Sørensen; Torsten Schmidt; Mechthilde Falkenhahn; Petra B Musholt; Stefan Theis; Philip J Larsen; Jens F Rehfeld; Niels Vrang; Jacob Jelsing; Tina Vilsbøll; Filip K Knop

doi:10.1002/oby.22973

Gut Mucosal Gene Expression and Metabolic Changes After Roux-en-Y Gastric Bypass Surgery

Obesity (Silver Spring). 2020 Nov;28(11):2163-2174. doi: 10.1002/oby.22973.

Authors

Tina Jorsal¹, Marie M Christensen^{1

2}, Brynjulf Mortensen¹, Eva B Nygaard³, Chen Zhang³, Kristoffer Rigbolt³, Erik Wandall⁴, Ebbe Langholz⁴, Steffen Friis⁴, Dorte Worm⁵, Andrea Floyd⁵, Frederik Helgstrand⁵, René K Støving⁶, Alin R Aldries⁷, Claus B Juhl⁷, Torben Østergaard⁸, Thomas Rydborg⁸, Julie L Forman⁹, Frederik Sørensen⁹, Torsten Schmidt¹⁰, Mechthilde Falkenhahn¹⁰, Petra B Musholt¹⁰, Stefan Theis¹⁰, Philip J Larsen¹⁰, Jens F Rehfeld¹¹, Niels Vrang³, Jacob Jelsing³, Tina Vilsbøll^{1

2

12}, Filip K Knop^{1

2

12

13}

Affiliations

¹ Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
² Steno Diabetes Center Copenhagen, Gentofte, Denmark.
³ Gubra, Hørsholm, Denmark.
⁴ Endoscopic Unit, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
⁵ Department of Gastrointestinal Surgery, Zealand University Hospital, Køge, Denmark.
⁶ Elite Research Center for Medical Endocrinology & Center for Eating Disorders, Odense University Hospital, Odense, Denmark.
⁷ Department of Medicine, South West Jutland Hospital, Esbjerg, Denmark.
⁸ Medical Unit, Viborg Regional Hospital, Viborg, Denmark.
⁹ Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
¹⁰ Sanofi Aventis, Frankfurt, Germany.
¹¹ Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
¹² Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
¹³ Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

PMID: 33150746
DOI: 10.1002/oby.22973

Abstract

Objective: Changes in the secretion of gut-derived peptide hormones have been associated with the metabolic benefits of Roux-en-Y gastric bypass (RYGB) surgery. In this study, the effects of RYGB on anthropometrics, postprandial plasma hormone responses, and mRNA expression in small intestinal mucosa biopsy specimens before and after RYGB were evaluated.

Methods: In a cross-sectional study, 20 individuals with obesity undergoing RYGB underwent mixed meal tests and upper enteroscopy with retrieval of small intestinal mucosa biopsy specimens 3 months before and after surgery. Concentrations of circulating gut and pancreatic hormones during mixed meal tests as well as full mRNA sequencing of biopsy specimens were evaluated.

Results: RYGB-induced improvements of body weight and composition, insulin resistance, and circulating cholesterols were accompanied by significant changes in postprandial plasma responses of pancreatic and gut hormones. Global gene expression analysis of biopsy specimens identified 2,437 differentially expressed genes after RYGB, including changes in genes that encode prohormones and G protein-coupled receptors.

Conclusions: RYGB affects the transcription of a wide range of genes, indicating that the observed beneficial metabolic effects of RYGB may rely on a changed expression of several genes in the gut. RYGB-induced changes in the expression of genes encoding signaling peptides and G protein-coupled receptors may disclose new gut-derived treatment targets against obesity and diabetes.

Trial registration: ClinicalTrials.gov NCT03093298.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Cross-Sectional Studies
Female
Gastric Bypass / methods*
Gastrointestinal Microbiome / genetics*
Gene Expression / genetics*
Humans
Male
Middle Aged

Associated data

ClinicalTrials.gov/NCT03093298