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

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dc.contributor.authorMalbert, C.H.
dc.contributor.authorHorowitz, M.
dc.contributor.authorYoung, R.L.
dc.date.issued2019
dc.description.abstractPurposes: 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 wholebody 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.
dc.description.statementofresponsibilityCharles-Henri Malbert, Michael Horowitz, Richard L. Young
dc.identifier.citationEuropean Journal of Nuclear Medicine and Molecular Imaging, 2019; 46(11):2380-2391
dc.identifier.doi10.1007/s00259-019-04430-4
dc.identifier.issn0340-6997
dc.identifier.issn1619-7089
dc.identifier.orcidMalbert, C.H. [0000-0002-0665-4545]
dc.identifier.orcidHorowitz, M. [0000-0002-0942-0306]
dc.identifier.orcidYoung, R.L. [0000-0001-5116-4951] [0009-0004-8274-9863]
dc.identifier.urihttps://hdl.handle.net/2440/145912
dc.language.isoen
dc.publisherSpringer
dc.rights© Springer-Verlag GmbH Germany, part of Springer Nature 2019
dc.source.urihttps://doi.org/10.1007/s00259-019-04430-4
dc.subjectBrain connectivity; Compartmental analysis; Glucose uptake; Insulin sensitivity; Miniature pig; Statistical parameter mapping; Sweeteners
dc.subject.meshAmygdala
dc.subject.meshHippocampus
dc.subject.meshFrontal Lobe
dc.subject.meshAdipose Tissue
dc.subject.meshAnimals
dc.subject.meshSwine
dc.subject.meshSwine, Miniature
dc.subject.meshInsulin Resistance
dc.subject.meshObesity
dc.subject.meshDisease Models, Animal
dc.subject.meshThiazines
dc.subject.meshInsulin
dc.subject.meshFluorodeoxyglucose F18
dc.subject.meshGlucose
dc.subject.meshSucrose
dc.subject.meshSweetening Agents
dc.subject.meshTomography, X-Ray Computed
dc.subject.meshBody Composition
dc.subject.meshAnimal Feed
dc.subject.meshFemale
dc.subject.meshMale
dc.titleLow-calorie sweeteners augment tissue-specific insulin sensitivity in a large animal model of obesity
dc.typeJournal article
pubs.publication-statusPublished

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