Loss of Sucrase-Isomaltase Function Increases Acetate Levels and Improves Metabolic Health in Greenlandic Cohorts.

Acetates Animals Carbohydrate Metabolism, Inborn Errors Dietary Sucrose / adverse effects Humans Mice Oligo-1,6-Glucosidase Sucrase-Isomaltase Complex / deficiency
Drug Target Genetics Loss of Function Metabolic Health Sucrase-Isomaltase

Journal

Gastroenterology
ISSN: 1528-0012
Titre abrégé: Gastroenterology
Pays: United States
ID NLM: 0374630

Informations de publication

Date de publication:
04 2022
Historique:
received: 01 03 2021
revised: 01 12 2021
accepted: 02 12 2021
pubmed: 17 12 2021
medline: 3 5 2022
entrez: 16 12 2021
Statut: ppublish

Résumé

The sucrase-isomaltase (SI) c.273_274delAG loss-of-function variant is common in Arctic populations and causes congenital sucrase-isomaltase deficiency, which is an inability to break down and absorb sucrose and isomaltose. Children with this condition experience gastrointestinal symptoms when dietary sucrose is introduced. We aimed to describe the health of adults with sucrase-isomaltase deficiency. The association between c.273_274delAG and phenotypes related to metabolic health was assessed in 2 cohorts of Greenlandic adults (n = 4922 and n = 1629). A sucrase-isomaltase knockout (Sis-KO) mouse model was used to further elucidate the findings. Homozygous carriers of the variant had a markedly healthier metabolic profile than the remaining population, including lower body mass index (β [standard error], -2.0 [0.5] kg/m These results suggest that sucrase-isomaltase constitutes a promising drug target for improvement of metabolic health, and that the health benefits are mediated by reduced dietary sucrose uptake and possibly also by higher levels of circulating acetate.

Sections du résumé

BACKGROUND & AIMS
The sucrase-isomaltase (SI) c.273_274delAG loss-of-function variant is common in Arctic populations and causes congenital sucrase-isomaltase deficiency, which is an inability to break down and absorb sucrose and isomaltose. Children with this condition experience gastrointestinal symptoms when dietary sucrose is introduced. We aimed to describe the health of adults with sucrase-isomaltase deficiency.
METHODS
The association between c.273_274delAG and phenotypes related to metabolic health was assessed in 2 cohorts of Greenlandic adults (n = 4922 and n = 1629). A sucrase-isomaltase knockout (Sis-KO) mouse model was used to further elucidate the findings.
RESULTS
Homozygous carriers of the variant had a markedly healthier metabolic profile than the remaining population, including lower body mass index (β [standard error], -2.0 [0.5] kg/m
CONCLUSIONS
These results suggest that sucrase-isomaltase constitutes a promising drug target for improvement of metabolic health, and that the health benefits are mediated by reduced dietary sucrose uptake and possibly also by higher levels of circulating acetate.

Identifiants

DOI: 10.1053/j.gastro.2021.12.236 PMID: 34914943
pubmed: 34914943
pii: S0016-5085(21)04065-8
doi: 10.1053/j.gastro.2021.12.236
pii:
doi:

Substances chimiques

Acetates 0
Dietary Sucrose 0
Sucrase-Isomaltase Complex EC 3.2.1.-
Oligo-1,6-Glucosidase EC 3.2.1.10

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

1171-1182.e3

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Auteurs

Mette K Andersen (MK)

Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Line Skotte (L)

Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.

Emil Jørsboe (E)

Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Section for Computational and RNA Biology, Department of Biology, University of Copenhagen, Copenhagen, Denmark.

Ryan Polito (R)

Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Frederik F Stæger (FF)

Section for Computational and RNA Biology, Department of Biology, University of Copenhagen, Copenhagen, Denmark.

Peter Aldiss (P)

Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Kristian Hanghøj (K)

Section for Computational and RNA Biology, Department of Biology, University of Copenhagen, Copenhagen, Denmark.

Ryan K Waples (RK)

Section for Computational and RNA Biology, Department of Biology, University of Copenhagen, Copenhagen, Denmark.

Cindy G Santander (CG)

Section for Computational and RNA Biology, Department of Biology, University of Copenhagen, Copenhagen, Denmark.

Niels Grarup (N)

Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Inger K Dahl-Petersen (IK)

National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark; Steno Diabetes Center Copenhagen, Gentofte, Denmark.

Lars J Diaz (LJ)

Steno Diabetes Center Copenhagen, Gentofte, Denmark.

Maria Overvad (M)

Steno Diabetes Center Copenhagen, Gentofte, Denmark.

Ninna K Senftleber (NK)

Section for Computational and RNA Biology, Department of Biology, University of Copenhagen, Copenhagen, Denmark; Steno Diabetes Center Copenhagen, Gentofte, Denmark.

Bolette Søborg (B)

Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.

Christina V L Larsen (CVL)

National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark; Greenland Centre for Health Research, University of Greenland, Nuuk, Greenland.

Clara Lemoine (C)

Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Oluf Pedersen (O)

Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Bjarke Feenstra (B)

Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.

Peter Bjerregaard (P)

National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark.

Mads Melbye (M)

Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Medicine, Stanford University School of Medicine, Stanford, California.

Marit E Jørgensen (ME)

National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark; Steno Diabetes Center Copenhagen, Gentofte, Denmark; Greenland Centre for Health Research, University of Greenland, Nuuk, Greenland.

Nils J Færgeman (NJ)

Department of Biochemistry and Molecular Biology, Villum Center for Bioanalytical Sciences, University of Southern Denmark, Odense, Denmark.

Anders Koch (A)

Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark; Greenland Centre for Health Research, University of Greenland, Nuuk, Greenland; Department of Infectious Diseases, Rigshospitalet University Hospital, Copenhagen, Denmark.

Thomas Moritz (T)

Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Matthew P Gillum (MP)

Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Ida Moltke (I)

Section for Computational and RNA Biology, Department of Biology, University of Copenhagen, Copenhagen, Denmark. Electronic address: ida@binf.ku.dk.

Torben Hansen (T)

Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. Electronic address: torben.hansen@sund.ku.dk.

Anders Albrechtsen (A)

Section for Computational and RNA Biology, Department of Biology, University of Copenhagen, Copenhagen, Denmark. Electronic address: albrecht@binf.ku.dk.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Lipides › Acides gras › Acides gras volatils › Acétates › Loss of Sucrase-Isomaltase Function Increases...
questionsmedicales.fr › Eucaryotes › Animaux › Loss of Sucrase-Isomaltase Function Increases...
questionsmedicales.fr › Maladies métaboliques et nutritionnelles › Maladies métaboliques › Erreurs innées du métabolisme › Erreurs innées du métabolisme glucidique › Loss of Sucrase-Isomaltase Function Increases...
questionsmedicales.fr › Aliments et boissons › Aliments › Ingrédients alimentaires › Additifs alimentaires › Aromatisants › Édulcorants › Édulcorants nutritifs › Saccharose alimentaire › Loss of Sucrase-Isomaltase Function Increases...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Loss of Sucrase-Isomaltase Function Increases...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Loss of Sucrase-Isomaltase Function Increases...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Glycosidases › Oligo-1,6-glucosidase › Loss of Sucrase-Isomaltase Function Increases...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Complexes multienzymatiques › Sucrase-isomaltase › Loss of Sucrase-Isomaltase Function Increases...