Long-term artificial sweetener acesulfame potassium treatment alters neurometabolic functions in C57BL/6J mice.

Wei-Na Cong,Rebecca Turkin,Stuart Maudsley,Ruin Moaddel,Vilhelm A Bohr,William H Wood,Caitlin M Daimon,Rui Wang,Kevin G Becker,Huan Cai,Bronwen Martin,Morten Scheibye-Knudsen

doi:10.1371/journal.pone.0070257

Abstract

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.

Highlights

The epidemic of obesity and diabetes is currently one of the most important healthcare issues for both developed and emerging nations [1]
Our study demonstrated that long-term (40 weeks) acesulfame K (ACK) ingestion elicited a moderate and limited influence on energy metabolic homeostasis such as alterations in levels of insulin and leptin with unclear clinical implications; most interestingly, the chronic intake of ACK significantly resulted in an impaired learning ability, which was potentially associated with deterioration of ‘neurometabolic’ functions in the brain
Physiological Effects of Extended ACK Ingestion As the tongue is one of the major peripheral organs responding to artificial sweeteners, we first investigated the taste responsivity of C57BL/6J (WT) mice to ACK-sweetened water using a brief access taste testing protocol

Summary

Introduction

The epidemic of obesity and diabetes is currently one of the most important healthcare issues for both developed and emerging nations [1]. To limit excessive calorie intake, the use of artificial sweeteners has accelerated in recent decades. Between 1999 and 2004, more than 6000 new artificial sweetener-containing products were launched in the US alone [2]. Non-nutritive artificial sweeteners are considered to possess an ability to satisfy sweet taste sensation, while not contributing to caloric intake. 5 of these non-nutritive artificial sweeteners, acesulfame potassium (ACK), sucralose, aspartame, saccharin and neotame, are approved by the FDA [3]. ACK, discovered in 1967 [4], is approximately 200 times sweeter than table sugar. ACK has been approved for use in a variety of food products including carbonated drinks, baking products, baby food and frozen food. All currently approved non-nutritive sweeteners are recognized as safe, according to a 2004 American Dietetic Association report [5]

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Results

Conclusion