Loss of sucrase-isomaltase function increases acetate levels and improves metabolic health in Greenlandic cohorts

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Loss of sucrase-isomaltase function increases acetate levels and improves metabolic health in Greenlandic cohorts. / Andersen, Mette K.; Skotte, Line; Jørsboe, Emil; Polito, Ryan; Stæger, Frederik F.; Aldiss, Peter; Hanghøj, Kristian; Waples, Ryan K.; Santander, Cindy G.; Grarup, Niels; Dahl-Petersen, Inger K.; Diaz, Lars J.; Overvad, Maria; Senftleber, Ninna K.; Søborg, Bolette; Larsen, Christina V. L.; Lemoine, Clara; Pedersen, Oluf; Feenstra, Bjarke; Bjerregaard, Peter; Melbye, Mads; Jørgensen, Marit E.; Færgeman, Nils J.; Koch, Anders; Moritz, Thomas; Gillum, Matthew P.; Moltke, Ida; Hansen, Torben; Albrechtsen, Anders.

In: Gastroenterology, Vol. 162, No. 4, 2022, p. 1171-1182.e3.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Andersen, MK, Skotte, L, Jørsboe, E, Polito, R, Stæger, FF, Aldiss, P, Hanghøj, K, Waples, RK, Santander, CG, Grarup, N, Dahl-Petersen, IK, Diaz, LJ, Overvad, M, Senftleber, NK, Søborg, B, Larsen, CVL, Lemoine, C, Pedersen, O, Feenstra, B, Bjerregaard, P, Melbye, M, Jørgensen, ME, Færgeman, NJ, Koch, A, Moritz, T, Gillum, MP, Moltke, I, Hansen, T & Albrechtsen, A 2022, 'Loss of sucrase-isomaltase function increases acetate levels and improves metabolic health in Greenlandic cohorts', Gastroenterology, vol. 162, no. 4, pp. 1171-1182.e3. https://doi.org/10.1053/j.gastro.2021.12.236

APA

Andersen, M. K., Skotte, L., Jørsboe, E., Polito, R., Stæger, F. F., Aldiss, P., Hanghøj, K., Waples, R. K., Santander, C. G., Grarup, N., Dahl-Petersen, I. K., Diaz, L. J., Overvad, M., Senftleber, N. K., Søborg, B., Larsen, C. V. L., Lemoine, C., Pedersen, O., Feenstra, B., ... Albrechtsen, A. (2022). Loss of sucrase-isomaltase function increases acetate levels and improves metabolic health in Greenlandic cohorts. Gastroenterology, 162(4), 1171-1182.e3. https://doi.org/10.1053/j.gastro.2021.12.236

Vancouver

Andersen MK, Skotte L, Jørsboe E, Polito R, Stæger FF, Aldiss P et al. Loss of sucrase-isomaltase function increases acetate levels and improves metabolic health in Greenlandic cohorts. Gastroenterology. 2022;162(4):1171-1182.e3. https://doi.org/10.1053/j.gastro.2021.12.236

Author

Andersen, Mette K. ; Skotte, Line ; Jørsboe, Emil ; Polito, Ryan ; Stæger, Frederik F. ; Aldiss, Peter ; Hanghøj, Kristian ; Waples, Ryan K. ; Santander, Cindy G. ; Grarup, Niels ; Dahl-Petersen, Inger K. ; Diaz, Lars J. ; Overvad, Maria ; Senftleber, Ninna K. ; Søborg, Bolette ; Larsen, Christina V. L. ; Lemoine, Clara ; Pedersen, Oluf ; Feenstra, Bjarke ; Bjerregaard, Peter ; Melbye, Mads ; Jørgensen, Marit E. ; Færgeman, Nils J. ; Koch, Anders ; Moritz, Thomas ; Gillum, Matthew P. ; Moltke, Ida ; Hansen, Torben ; Albrechtsen, Anders. / Loss of sucrase-isomaltase function increases acetate levels and improves metabolic health in Greenlandic cohorts. In: Gastroenterology. 2022 ; Vol. 162, No. 4. pp. 1171-1182.e3.

Bibtex

@article{85e14c2a87d34d17bb76800a71a7620b,
title = "Loss of sucrase-isomaltase function increases acetate levels and improves metabolic health in Greenlandic cohorts",
abstract = "BACKGROUND & AIMS: The sucrase-isomaltase (SI) c.273_274delAG loss-of-function variant is common in Arctic populations and causes congenital sucrase-isomaltase deficiency, an inability to breakdown and absorb sucrose and isomaltose. Children with this condition experience gastrointestinal symptoms, when dietary sucrose is introduced. Here we aimed to describe the health of adults with sucrase-isomaltase deficiency.METHODS: Association between c.273_274delAG and phenotypes related to metabolic health was assessed in two cohorts of Greenlandic adults (N=4,922 and N=1,629). A sucrase-isomaltase knock-out (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 BMI (β (SE), -2.0 kg/m2 (0.5), P=3.1x10-5), body weight (-4.8 kg (1.4), P=5.1x10-4), fat percentage (-3.3% (1.0), P=3.7x10-4), fasting triglyceride (-0.27 mmol/L (0.07), P=2.3x10-6), and remnant cholesterol (-0.11 mmol/L (0.03), P=4.2x10-5). Further analyses suggested that this was likely mediated partly by higher circulating levels of acetate observed in homozygous carriers (0.056 mmol/L (0.002), P=2.1x10-26), and partly by reduced sucrose uptake, but not lower caloric intake. These findings were verified in Sis-KO mice, which compared to wild-type mice were leaner on a sucrose-containing diet, despite similar caloric intake, had significantly higher plasma acetate levels in response to a sucrose gavage, and had lower plasma glucose level in response to a sucrose-tolerance test.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.",
author = "Andersen, {Mette K.} and Line Skotte and Emil J{\o}rsboe and Ryan Polito and St{\ae}ger, {Frederik F.} and Peter Aldiss and Kristian Hangh{\o}j and Waples, {Ryan K.} and Santander, {Cindy G.} and Niels Grarup and Dahl-Petersen, {Inger K.} and Diaz, {Lars J.} and Maria Overvad and Senftleber, {Ninna K.} and Bolette S{\o}borg and Larsen, {Christina V. L.} and Clara Lemoine and Oluf Pedersen and Bjarke Feenstra and Peter Bjerregaard and Mads Melbye and J{\o}rgensen, {Marit E.} and F{\ae}rgeman, {Nils J.} and Anders Koch and Thomas Moritz and Gillum, {Matthew P.} and Ida Moltke and Torben Hansen and Anders Albrechtsen",
note = "Copyright {\textcopyright} 2021 The Authors. Published by Elsevier Inc. All rights reserved.",
year = "2022",
doi = "10.1053/j.gastro.2021.12.236",
language = "English",
volume = "162",
pages = "1171--1182.e3",
journal = "Gastroenterology",
issn = "0016-5085",
publisher = "Elsevier",
number = "4",

}

RIS

TY - JOUR

T1 - Loss of sucrase-isomaltase function increases acetate levels and improves metabolic health in Greenlandic cohorts

AU - Andersen, Mette K.

AU - Skotte, Line

AU - Jørsboe, Emil

AU - Polito, Ryan

AU - Stæger, Frederik F.

AU - Aldiss, Peter

AU - Hanghøj, Kristian

AU - Waples, Ryan K.

AU - Santander, Cindy G.

AU - Grarup, Niels

AU - Dahl-Petersen, Inger K.

AU - Diaz, Lars J.

AU - Overvad, Maria

AU - Senftleber, Ninna K.

AU - Søborg, Bolette

AU - Larsen, Christina V. L.

AU - Lemoine, Clara

AU - Pedersen, Oluf

AU - Feenstra, Bjarke

AU - Bjerregaard, Peter

AU - Melbye, Mads

AU - Jørgensen, Marit E.

AU - Færgeman, Nils J.

AU - Koch, Anders

AU - Moritz, Thomas

AU - Gillum, Matthew P.

AU - Moltke, Ida

AU - Hansen, Torben

AU - Albrechtsen, Anders

N1 - Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2022

Y1 - 2022

N2 - BACKGROUND & AIMS: The sucrase-isomaltase (SI) c.273_274delAG loss-of-function variant is common in Arctic populations and causes congenital sucrase-isomaltase deficiency, an inability to breakdown and absorb sucrose and isomaltose. Children with this condition experience gastrointestinal symptoms, when dietary sucrose is introduced. Here we aimed to describe the health of adults with sucrase-isomaltase deficiency.METHODS: Association between c.273_274delAG and phenotypes related to metabolic health was assessed in two cohorts of Greenlandic adults (N=4,922 and N=1,629). A sucrase-isomaltase knock-out (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 BMI (β (SE), -2.0 kg/m2 (0.5), P=3.1x10-5), body weight (-4.8 kg (1.4), P=5.1x10-4), fat percentage (-3.3% (1.0), P=3.7x10-4), fasting triglyceride (-0.27 mmol/L (0.07), P=2.3x10-6), and remnant cholesterol (-0.11 mmol/L (0.03), P=4.2x10-5). Further analyses suggested that this was likely mediated partly by higher circulating levels of acetate observed in homozygous carriers (0.056 mmol/L (0.002), P=2.1x10-26), and partly by reduced sucrose uptake, but not lower caloric intake. These findings were verified in Sis-KO mice, which compared to wild-type mice were leaner on a sucrose-containing diet, despite similar caloric intake, had significantly higher plasma acetate levels in response to a sucrose gavage, and had lower plasma glucose level in response to a sucrose-tolerance test.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.

AB - BACKGROUND & AIMS: The sucrase-isomaltase (SI) c.273_274delAG loss-of-function variant is common in Arctic populations and causes congenital sucrase-isomaltase deficiency, an inability to breakdown and absorb sucrose and isomaltose. Children with this condition experience gastrointestinal symptoms, when dietary sucrose is introduced. Here we aimed to describe the health of adults with sucrase-isomaltase deficiency.METHODS: Association between c.273_274delAG and phenotypes related to metabolic health was assessed in two cohorts of Greenlandic adults (N=4,922 and N=1,629). A sucrase-isomaltase knock-out (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 BMI (β (SE), -2.0 kg/m2 (0.5), P=3.1x10-5), body weight (-4.8 kg (1.4), P=5.1x10-4), fat percentage (-3.3% (1.0), P=3.7x10-4), fasting triglyceride (-0.27 mmol/L (0.07), P=2.3x10-6), and remnant cholesterol (-0.11 mmol/L (0.03), P=4.2x10-5). Further analyses suggested that this was likely mediated partly by higher circulating levels of acetate observed in homozygous carriers (0.056 mmol/L (0.002), P=2.1x10-26), and partly by reduced sucrose uptake, but not lower caloric intake. These findings were verified in Sis-KO mice, which compared to wild-type mice were leaner on a sucrose-containing diet, despite similar caloric intake, had significantly higher plasma acetate levels in response to a sucrose gavage, and had lower plasma glucose level in response to a sucrose-tolerance test.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.

U2 - 10.1053/j.gastro.2021.12.236

DO - 10.1053/j.gastro.2021.12.236

M3 - Journal article

C2 - 34914943

VL - 162

SP - 1171-1182.e3

JO - Gastroenterology

JF - Gastroenterology

SN - 0016-5085

IS - 4

ER -

ID: 288853848