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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 11/2019

01-10-2019 | Obesity | Original Article

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

Authors: Charles-Henri Malbert, Michael Horowitz, Richard L. Young

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 11/2019

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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.
Appendix
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Metadata
Title
Low-calorie sweeteners augment tissue-specific insulin sensitivity in a large animal model of obesity
Authors
Charles-Henri Malbert
Michael Horowitz
Richard L. Young
Publication date
01-10-2019
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 11/2019
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-019-04430-4

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