PMID- 31338548
OWN - NLM
STAT- MEDLINE
DCOM- 20201016
LR  - 20210110
IS  - 1619-7089 (Electronic)
IS  - 1619-7070 (Linking)
VI  - 46
IP  - 11
DP  - 2019 Oct
TI  - Low-calorie sweeteners augment tissue-specific insulin sensitivity in a large 
      animal model of obesity.
PG  - 2380-2391
LID - 10.1007/s00259-019-04430-4 [doi]
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 (18)FDG, 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 (18)FDG 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  approximately  20% without causing weight 
      gain, and reduced insulin clearance by  approximately  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.
FAU - Malbert, Charles-Henri
AU  - Malbert CH
AUID- ORCID: 0000-0002-0665-4545
AD  - Aniscan Unit, Department of Human Nutrition, INRA, 16, le clos, 35590, 
      Saint-Gilles, France. charles-henri.malbert@inra.fr.
FAU - Horowitz, Michael
AU  - Horowitz M
AD  - Center of Research Excellence in Translating Nutrition to Good Health, The 
      University of Adelaide, Adelaide, 5005, Australia.
FAU - Young, Richard L
AU  - Young RL
AD  - Center of Research Excellence in Translating Nutrition to Good Health, The 
      University of Adelaide, Adelaide, 5005, Australia.
AD  - Nutrition & Metabolism, South Australia Health & Medical Research Institute, 
      Adelaide, 5000, Australia.
LA  - eng
PT  - Journal Article
DEP - 20190724
PL  - Germany
TA  - Eur J Nucl Med Mol Imaging
JT  - European journal of nuclear medicine and molecular imaging
JID - 101140988
RN  - 0 (Insulin)
RN  - 0 (Sweetening Agents)
RN  - 0 (Thiazines)
RN  - 0Z5B2CJX4D (Fluorodeoxyglucose F18)
RN  - 57-50-1 (Sucrose)
RN  - 96K6UQ3ZD4 (trichlorosucrose)
RN  - IY9XDZ35W2 (Glucose)
RN  - MA3UYZ6K1H (acetosulfame)
SB  - IM
MH  - Adipose Tissue/metabolism
MH  - Amygdala/diagnostic imaging
MH  - Animal Feed
MH  - Animals
MH  - Body Composition
MH  - Disease Models, Animal
MH  - Female
MH  - Fluorodeoxyglucose F18
MH  - Frontal Lobe/diagnostic imaging
MH  - Glucose/metabolism
MH  - Hippocampus/diagnostic imaging
MH  - Insulin/*metabolism
MH  - Insulin Resistance
MH  - Male
MH  - Obesity/*metabolism/*physiopathology
MH  - Sucrose/analogs & derivatives/pharmacology
MH  - Sweetening Agents/*pharmacology
MH  - Swine
MH  - Swine, Miniature
MH  - Thiazines/pharmacology
MH  - Tomography, X-Ray Computed
OTO - NOTNLM
OT  - Brain connectivity
OT  - Compartmental analysis
OT  - Glucose uptake
OT  - Insulin sensitivity
OT  - Miniature pig
OT  - Statistical parameter mapping
OT  - Sweeteners
EDAT- 2019/07/25 06:00
MHDA- 2020/10/21 06:00
CRDT- 2019/07/25 06:00
PHST- 2019/02/11 00:00 [received]
PHST- 2019/07/09 00:00 [accepted]
PHST- 2019/07/25 06:00 [pubmed]
PHST- 2020/10/21 06:00 [medline]
PHST- 2019/07/25 06:00 [entrez]
AID - 10.1007/s00259-019-04430-4 [pii]
AID - 10.1007/s00259-019-04430-4 [doi]
PST - ppublish
SO  - Eur J Nucl Med Mol Imaging. 2019 Oct;46(11):2380-2391. doi: 
      10.1007/s00259-019-04430-4. Epub 2019 Jul 24.