Long-term artificial sweetener acesulfame potassium treatment alters neurometabolic functions in C57BL/6J mice.
With the prevalence of obesity, artificial, non-nutritive sweeteners have been widely used as dietary supplements that provide sweet taste without excessive caloric load. In order to better understand the overall actions of artificial sweeteners, especially when they are chronically used, we investigated the peripheral and central nervous system effects of protracted exposure to a widely used artificial sweetener, acesulfame K (ACK). We found that extended ACK exposure (40 weeks) in normal C57BL/6J mice demonstrated a moderate and limited influence on metabolic homeostasis, including altering fasting insulin and leptin levels, pancreatic islet size and lipid levels, without affecting insulin sensitivity and bodyweight. Interestingly, impaired cognitive memory functions (evaluated by Morris Water Maze and Novel Objective Preference tests) were found in ACK-treated C57BL/6J mice, while no differences in motor function and anxiety levels were detected. The generation of an ACK-induced neurological phenotype was associated with metabolic dysregulation (glycolysis inhibition and functional ATP depletion) and neurosynaptic abnormalities (dysregulation of TrkB-mediated BDNF and Akt/Erk-mediated cell growth/survival pathway) in hippocampal neurons. Our data suggest that chronic use of ACK could affect cognitive functions, potentially via altering neuro-metabolic functions in male C57BL/6J mice.
Metabolism Unit, Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, Maryland, United States of America.
Wei-na
WN
Cong
Rui
R
Wang
Huan
H
Cai
Caitlin M
CM
Daimon
Morten
M
Scheibye-Knudsen
Vilhelm A
VA
Bohr
Rebecca
R
Turkin
William H
WH
Wood
Kevin G
KG
Becker
Ruin
R
Moaddel
Stuart
S
Maudsley
Bronwen
B
Martin
D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003071:Cognition / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000254:growth & development; D020738:Leptin / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009929:Organ Size / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D020813:Receptor, trkB / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013549:Sweetening Agents / Q000494:pharmacology*; D013843:Thiazines / Q000494:pharmacology*; D013997:Time Factors; D059467:Transcriptome / Q000187:drug effects / Q000235:genetics
D007328:Insulin; D020738:Leptin; D043562:Receptors, G-Protein-Coupled; D013549:Sweetening Agents; D013843:Thiazines; C431926:taste receptors, type 1; D020813:Receptor, trkB; C006362:acetosulfame