The Influence of Sugar and Artificial Sweeteners on Vascular Health during the Onset and Progression of Diabetes

Abstract

As diabetes and obesity become a rising worldwide heath concern there has been an increased awareness of environmental factors, such as diet, that are contributing to the problem. The negative implications of consuming high amounts of dietary sugar on overall health have long been linked to diabetes, obesity, cardiovascular disease, and other systemic health problems. However, it was not until recently that the negative impact of consuming non‐caloric artificial sweeteners in the place of sugar had been increasingly recognized as a potential contributor to the dramatic increase in diabetes and obesity, along with the associated complications. This study tested the response of the vascular endothelium in vitro and the in vivo response of a diabetes susceptible BB‐DR rat model to glucose, aspartame, and acesulfame potassium supplementation through the use of high‐throughput ‘omics' analyses coupled with functional testing. We have demonstrated that an acute in vitro treatment of rat microvascular endothelial cells with high glucose (25 mM) results in impairment of through glycosylation as exhibited by a restored function with PNGaseF enzymatic removal of N‐glycosylations (p<0.05). Conversely, artificial sweetener treatments also exhibited endothelial impairment in an in vitro tube formation assay (p<0.05); however, gene expression analyses suggested the mechanisms of dysfunction were through different mechanisms than the glucose treatment. Furthermore, through a site‐specific proteomic analysis we have identified 87 proteins significantly increased in N‐glycosylation and 143 in O‐glycosylation (p<0.05) on the endothelial cell surface following high glucose treatment as compared to normal glucose (4.5 mM); many targets related to vascular homeostasis. Those experiments have been supplemented with a comprehensive metabolomics analysis of plasma from an acute three week study on diabetes susceptible BB‐DR rats fed a high glucose, aspartame, or acesulfame potassium diet. Through this set of experiments we have identified unique signatures of alterations in lipid metabolism, among others, following artificial sweetener consumption. Overall, results of this study suggests that exposure to high glucose and artificial sweetener administration lead to unique mechanisms of vascular impairment and homeostatic alterations that may be important during the onset and progression of diabetes and obesity.Support or Funding InformationSupport for this project has been provided by the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases (K01‐DK105043 to BRH) and the Department of Biomedical Engineering at the Medical College of Wisconsin and Marquette University, Milwaukee, WI, USA.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.