Low-calorie sweeteners augment tissue-specific insulin sensitivity in a large animal model of obesity

Charles Henri Malbert, Michael Horowitz, Richard Young

Research output: Contribution to journalArticle

Abstract

Purposes: Whether low-calorie sweeteners (LCS), such as sucralose and acesulfame K, can alter glucose metabolism is uncertain, particularly given the inconsistent observations relating to insulin resistance in recent human trials. We hypothesized that these discrepancies are accounted for by the surrogate tools used to evaluate insulin resistance and that PET 18FDG, given its capacity to quantify insulin sensitivity in individual organs, would be more sensitive in identifying changes in glucose metabolism. Accordingly, we performed a comprehensive evaluation of the effects of LCS on whole-body and organ-specific glucose uptake and insulin sensitivity in a large animal model of morbid obesity. Methods: Twenty mini-pigs with morbid obesity were fed an obesogenic diet enriched with LCS (sucralose 1 mg/kg/day and acesulfame K 0.5 mg/kg/day, LCS diet group), or without LCS (control group), for 3 months. Glucose uptake and insulin sensitivity were determined for the duodenum, liver, skeletal muscle, adipose tissue and brain using dynamic PET 18FDG scanning together with direct measurement of arterial input function. Body composition was also measured using CT imaging and energy metabolism quantified with indirect calorimetry. Results: The LCS diet increased subcutaneous abdominal fat by ≈ 20% without causing weight gain, and reduced insulin clearance by ≈ 40%, while whole-body glucose uptake and insulin sensitivity were unchanged. In contrast, glucose uptake in the duodenum, liver and brain increased by 57, 66 and 29% relative to the control diet group (P < 0.05 for all), while insulin sensitivity increased by 53, 55 and 28% (P < 0.05 for all), respectively. In the brain, glucose uptake increased significantly only in the frontal cortex, associated with improved metabolic connectivity towards the hippocampus and the amygdala. Conclusions: In miniature pigs, the combination of sucralose and acesulfame K is biologically active. While not affecting whole-body insulin resistance, it increases insulin sensitivity and glucose uptake in specific tissues, mimicking the effects of obesity in the adipose tissue and in the brain.

LanguageEnglish
Pages2380-2391
Number of pages12
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume46
Issue number11
DOIs
Publication statusPublished - 1 Oct 2019

Keywords

  • Brain connectivity
  • Compartmental analysis
  • Glucose uptake
  • Insulin sensitivity
  • Miniature pig
  • Statistical parameter mapping
  • Sweeteners

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

@article{49d5a294e457475283e2483fcbe9cf50,
title = "Low-calorie sweeteners augment tissue-specific insulin sensitivity in a large animal model of obesity",
abstract = "Purposes: Whether low-calorie sweeteners (LCS), such as sucralose and acesulfame K, can alter glucose metabolism is uncertain, particularly given the inconsistent observations relating to insulin resistance in recent human trials. We hypothesized that these discrepancies are accounted for by the surrogate tools used to evaluate insulin resistance and that PET 18FDG, given its capacity to quantify insulin sensitivity in individual organs, would be more sensitive in identifying changes in glucose metabolism. Accordingly, we performed a comprehensive evaluation of the effects of LCS on whole-body and organ-specific glucose uptake and insulin sensitivity in a large animal model of morbid obesity. Methods: Twenty mini-pigs with morbid obesity were fed an obesogenic diet enriched with LCS (sucralose 1 mg/kg/day and acesulfame K 0.5 mg/kg/day, LCS diet group), or without LCS (control group), for 3 months. Glucose uptake and insulin sensitivity were determined for the duodenum, liver, skeletal muscle, adipose tissue and brain using dynamic PET 18FDG scanning together with direct measurement of arterial input function. Body composition was also measured using CT imaging and energy metabolism quantified with indirect calorimetry. Results: The LCS diet increased subcutaneous abdominal fat by ≈ 20{\%} without causing weight gain, and reduced insulin clearance by ≈ 40{\%}, while whole-body glucose uptake and insulin sensitivity were unchanged. In contrast, glucose uptake in the duodenum, liver and brain increased by 57, 66 and 29{\%} relative to the control diet group (P < 0.05 for all), while insulin sensitivity increased by 53, 55 and 28{\%} (P < 0.05 for all), respectively. In the brain, glucose uptake increased significantly only in the frontal cortex, associated with improved metabolic connectivity towards the hippocampus and the amygdala. Conclusions: In miniature pigs, the combination of sucralose and acesulfame K is biologically active. While not affecting whole-body insulin resistance, it increases insulin sensitivity and glucose uptake in specific tissues, mimicking the effects of obesity in the adipose tissue and in the brain.",
keywords = "Brain connectivity, Compartmental analysis, Glucose uptake, Insulin sensitivity, Miniature pig, Statistical parameter mapping, Sweeteners",
author = "Malbert, {Charles Henri} and Michael Horowitz and Richard Young",
year = "2019",
month = "10",
day = "1",
doi = "10.1007/s00259-019-04430-4",
language = "English",
volume = "46",
pages = "2380--2391",
journal = "European Journal of Nuclear Medicine and Molecular Imaging",
issn = "1619-7070",
publisher = "Springer Verlag",
number = "11",

}

Low-calorie sweeteners augment tissue-specific insulin sensitivity in a large animal model of obesity. / Malbert, Charles Henri; Horowitz, Michael; Young, Richard.

In: European Journal of Nuclear Medicine and Molecular Imaging, Vol. 46, No. 11, 01.10.2019, p. 2380-2391.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Low-calorie sweeteners augment tissue-specific insulin sensitivity in a large animal model of obesity

AU - Malbert, Charles Henri

AU - Horowitz, Michael

AU - Young, Richard

PY - 2019/10/1

Y1 - 2019/10/1

N2 - Purposes: Whether low-calorie sweeteners (LCS), such as sucralose and acesulfame K, can alter glucose metabolism is uncertain, particularly given the inconsistent observations relating to insulin resistance in recent human trials. We hypothesized that these discrepancies are accounted for by the surrogate tools used to evaluate insulin resistance and that PET 18FDG, given its capacity to quantify insulin sensitivity in individual organs, would be more sensitive in identifying changes in glucose metabolism. Accordingly, we performed a comprehensive evaluation of the effects of LCS on whole-body and organ-specific glucose uptake and insulin sensitivity in a large animal model of morbid obesity. Methods: Twenty mini-pigs with morbid obesity were fed an obesogenic diet enriched with LCS (sucralose 1 mg/kg/day and acesulfame K 0.5 mg/kg/day, LCS diet group), or without LCS (control group), for 3 months. Glucose uptake and insulin sensitivity were determined for the duodenum, liver, skeletal muscle, adipose tissue and brain using dynamic PET 18FDG scanning together with direct measurement of arterial input function. Body composition was also measured using CT imaging and energy metabolism quantified with indirect calorimetry. Results: The LCS diet increased subcutaneous abdominal fat by ≈ 20% without causing weight gain, and reduced insulin clearance by ≈ 40%, while whole-body glucose uptake and insulin sensitivity were unchanged. In contrast, glucose uptake in the duodenum, liver and brain increased by 57, 66 and 29% relative to the control diet group (P < 0.05 for all), while insulin sensitivity increased by 53, 55 and 28% (P < 0.05 for all), respectively. In the brain, glucose uptake increased significantly only in the frontal cortex, associated with improved metabolic connectivity towards the hippocampus and the amygdala. Conclusions: In miniature pigs, the combination of sucralose and acesulfame K is biologically active. While not affecting whole-body insulin resistance, it increases insulin sensitivity and glucose uptake in specific tissues, mimicking the effects of obesity in the adipose tissue and in the brain.

AB - Purposes: Whether low-calorie sweeteners (LCS), such as sucralose and acesulfame K, can alter glucose metabolism is uncertain, particularly given the inconsistent observations relating to insulin resistance in recent human trials. We hypothesized that these discrepancies are accounted for by the surrogate tools used to evaluate insulin resistance and that PET 18FDG, given its capacity to quantify insulin sensitivity in individual organs, would be more sensitive in identifying changes in glucose metabolism. Accordingly, we performed a comprehensive evaluation of the effects of LCS on whole-body and organ-specific glucose uptake and insulin sensitivity in a large animal model of morbid obesity. Methods: Twenty mini-pigs with morbid obesity were fed an obesogenic diet enriched with LCS (sucralose 1 mg/kg/day and acesulfame K 0.5 mg/kg/day, LCS diet group), or without LCS (control group), for 3 months. Glucose uptake and insulin sensitivity were determined for the duodenum, liver, skeletal muscle, adipose tissue and brain using dynamic PET 18FDG scanning together with direct measurement of arterial input function. Body composition was also measured using CT imaging and energy metabolism quantified with indirect calorimetry. Results: The LCS diet increased subcutaneous abdominal fat by ≈ 20% without causing weight gain, and reduced insulin clearance by ≈ 40%, while whole-body glucose uptake and insulin sensitivity were unchanged. In contrast, glucose uptake in the duodenum, liver and brain increased by 57, 66 and 29% relative to the control diet group (P < 0.05 for all), while insulin sensitivity increased by 53, 55 and 28% (P < 0.05 for all), respectively. In the brain, glucose uptake increased significantly only in the frontal cortex, associated with improved metabolic connectivity towards the hippocampus and the amygdala. Conclusions: In miniature pigs, the combination of sucralose and acesulfame K is biologically active. While not affecting whole-body insulin resistance, it increases insulin sensitivity and glucose uptake in specific tissues, mimicking the effects of obesity in the adipose tissue and in the brain.

KW - Brain connectivity

KW - Compartmental analysis

KW - Glucose uptake

KW - Insulin sensitivity

KW - Miniature pig

KW - Statistical parameter mapping

KW - Sweeteners

UR - http://www.scopus.com/inward/record.url?scp=85069660386&partnerID=8YFLogxK

U2 - 10.1007/s00259-019-04430-4

DO - 10.1007/s00259-019-04430-4

M3 - Article

VL - 46

SP - 2380

EP - 2391

JO - European Journal of Nuclear Medicine and Molecular Imaging

T2 - European Journal of Nuclear Medicine and Molecular Imaging

JF - European Journal of Nuclear Medicine and Molecular Imaging

SN - 1619-7070

IS - 11

ER -