Long-Term Artificial Sweetener Acesulfame Potassium Treatment Alters Neurometabolic Functions in C57BL/6J Mice

PLoS One

Ruin Moaddel¹  Kevin G. Becker²  William H. Wood III²  Huan Cai³  Caitlin M. Daimon³  Rebecca Turkin³  Bronwen Martin³  Wei-na Cong³  Rui Wang³  Stuart Maudsley⁴  Vilhelm A. Bohr⁵  Morten Scheibye-Knudsen⁵ 

[1] Bioanalytical Chemistry and Drug Discovery Section, Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, Maryland, United States of America;Gene Expression and Genomics Unit, Laboratory of Genetics, National Institute on Aging, Baltimore, Maryland, United States of America;Metabolism Unit, Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, Maryland, United States of America;Receptor Pharmacology Unit, Laboratory of Neurosciences, National Institute on Aging, Baltimore, Maryland, United States of America;Section on DNA repair, Laboratory of Molecular Gerontology, National Institute on Aging, Baltimore, Maryland, United States of America

关键词: Taste;    Insulin;    Mouse models;    Central nervous system;    Cognitive impairment;    Leptin;    Hippocampus;    Glucose metabolism;   

DOI  :  10.1371/journal.pone.0070257

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY