Cardiometabolic Effects Associated with the Absorption of Intact Non‐caloric Artificial Sweeteners
Authors: Hoffmann Brian R. , Ronan George , Centeno Evelyn Granados , Danner Laura , Roethle Mark , Haspula Dhanush , Hessner Martin J. 
Published: June 2021

As the diabetes epidemic grows worldwide, there is a heightened awareness of how modern day diets may contribute to the increased incidence of the disease. To combat the dietary intake of sugar, there has been a drastic increase in the consumption of non‐caloric artificial sweeteners (NCAS) in everyday diets. However, a number of studies suggest that NCAS disrupt homeostatic processes and cause counterintuitive metabolic derangements that may contribute to disease. Conversely, there are limited duration studies focused on weight management suggesting the opposite, thus creating controversy. One confounding factor of studies in the field is the fact that the NCAS are very biochemically different, yet studies often generalize the compounds. Through a comprehensive metabolomics study, our laboratory has shown that acesulfame potassium (Ace‐K+; absorbed intact) accumulated in the plasma of BB‐DR rats (21±10 μM; N=6) following three‐week dietary supplementation as measured through a targeted mass spectrometry quantification, suggesting the need to examine the effects of the absorbed compounds. Therefore, the aim of this study was to test the hypothesis that the chronic consumption of diets rich in NCAS subtypes that are absorbed intact will lead to distinct cardiometabolic derangements that compound diabetes risk factors. To test this, rat cardiac microvascular cells (RCMVECs) derived from healthy Sprague‐Dawley rats were exposed to a dose‐range of Ace‐K+, sucralose, or stevioside for up to three weeks. The RCMVECs were tested for functional impairment via tube formation, cell viability, and reactive oxygen species (ROS) assays. Results varied between the NCAS groups; however, each treatment exhibited RCMVEC impairment in the in vitro tube formation and cell viability assays (p<0.05; N=3), but not in ROS formation. As the greatest effect was observed with Ace‐K+ treated RCMVECs, we performed qPCR on genes related to the development of diabetes. The qPCR analysis displayed significant differences in insulin signaling, glucose metabolism, and inflammatory regulatory genes (p<0.05; N=4). In a comprehensive metabolomics study in BB‐DR rat model, we also identified unique plasma signatures of alterations in energy and lipid metabolism in response to Ace‐K+. In further tests to examine the effects of chronic Ace‐K+ in relation to the onset of diabetes, we observed that a chronic Ace‐K+ diet accelerated the rate to onset of disease in the diabetes prone rat model (BB‐DP). Overall, results of this study suggests that the accumulation of absorbed NCAS have the potential to lead to cardiometabolic flux that may be important during the development of diabetes, especially in genetically susceptible individuals.Support or Funding InformationSupport was provided by the NIH–NIDDK (K01‐DK105043 to BRH), the Mayo Clinic MRC via a pilot award provide by the U24DK100469 grant, and the Department of Biomedical Engineering at the Medical College of Wisconsin and Marquette University.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.