Modified High-Density Lipoproteins by Artificial Sweetener, Aspartame, and Saccharin, Showed Loss of Anti-atherosclerotic Activity and Toxicity in Zebrafish

Abstract

Safety concerns have been raised regarding the association of chronic consumption of artificial sweeteners (ASs) with metabolic disorders, especially in the heart and brain. There has been no information on the in vivo physiological effects of AS consumption in lipoprotein metabolism. High-dosage treatment (final 25, 50, and 100 mM) with AS (aspartame, acesulfame K, and saccharin) to human high-density lipoprotein (HDL) induced loss of antioxidant ability along with elevated atherogenic effects. Aspartame-treated HDL3 (final 100 mM) almost all disappeared due to putative proteolytic degradation. Aspartame- and saccharin-treated HDL3 showed more enhanced cholesteryl ester transfer activity, while their antioxidant ability was disappeared. Microinjection of the modified HDL3 exacerbated the inflammatory death in zebrafish embryos in the presence of oxLDL. These results show that AS treatment impaired the beneficial functions of HDL, resulting in loss of antioxidant and anti-atherogenic activities. These results suggest that aspartame and saccharin could be toxic to the human circulation system as well as embryonic development via impairment of lipoprotein function.

Effects of the Particulate Matter2.5 (PM2.5) on Lipoprotein Metabolism, Uptake and Degradation, and Embryo Toxicity

“…Zebrafish embryos were treated with water extract of PM 2.5 (final 3 and 30 ppm, wt/vol) according to our previous report ( Kim et al, 2015a ), based on the assumption that all components of PM 2.5 were completely dissolved in the aqueous medium. In a preliminary study, we found that a final concentration of 3 ppm of PM 2.5 was lethal to zebrafish after 10-fold serial dilutions from 0.0003 to 300 ppm.…”

The oxidative stress in the liver of Carassius auratus exposed to acesulfame and its UV irradiance products

“…Although ACE was proved safe for human use by the US Food and Drug Administration (FDA), the public protection agencies in the European Union and China, it was reported that ACE may cause DNA damage in the bone marrow cells of mice (Bandyopadhyay et al 2008) and interfere with photosynthesis in plants (Subedi and Kannan 2014). Increased reactive oxygen species (ROS) production in zebrafish embryo and a higher embryo death rate was found when the fish were exposed to low g/L dosage ACE (Kim et al 2015). Some other ASs would cause developmental toxicity to Oryzias latipes (Lee and Wang 2015).…”

Atherogenicity of Monosaccharides, Disaccharides and Artificial Sweeteners in the Lipid-Laden Macrophage Model System: Cell Culture and Mice Studies

“…It was previously shown that high concentrations of aspartame and saccharin (25-100 mM) impaired the beneficial anti-atherogenic activities of HDL, induced embryonic toxicity and increased ROS production [30].…”

“…In atherosclerotic apolipoprotein E-deficient (apoE-/-) mice, consumption of aspartame-acesulfame K sweetened 'light' cola was found to accelerate the progression of atherosclerotic plaques and the accumulation of sub-endothelial lipid-laden macrophages [27,28]. Also, in vitro treatment of apoA-I or HDL with physiological concentrations of aspartame, acesulfame K, or saccharin resulted in their pro-oxidative and pro-atherogenic modifications [29,30]. On the other hand, consumption of stevioside by leptin and LDLR double knockout mice was reported to reduce the aortic plaque volume by decreasing the content of macrophages, lipids, and ox-LDL in the plaque [31].…”