title: 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.
authors.affiliation: School of Biotechnology, Yeungnam University, Gyeongsan, 712-749, Republic of Korea.
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Kim
authors.forename: Ki-Hoon
authors.initials: KH
authors.lastname: Park
authors.forename: Jihoe
authors.initials: J
authors.lastname: Kim
authors.forename: Inho
authors.initials: I
authors.lastname: Choi
authors.forename: Kyung-Hyun
authors.initials: KH
authors.lastname: Cho
mesh_terms: D000818:Animals; D001218:Aspartame / Q000633:toxicity; D050197:Atherosclerosis / Q000378:metabolism*; D053480:Cholesterol Ester Transfer Proteins / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008075:Lipoproteins, HDL / Q000302:isolation & purification / Q000378:metabolism*; D053440:Lipoproteins, HDL3 / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress; D017382:Reactive Oxygen Species; D012439:Saccharin / Q000633:toxicity; D013549:Sweetening Agents / Q000633:toxicity*; D015027:Zebrafish / Q000196:embryology*
chemical_list: D053480:Cholesterol Ester Transfer Proteins; D008075:Lipoproteins, HDL; D053440:Lipoproteins, HDL3; D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; D013549:Sweetening Agents; D012439:Saccharin; D001218:Aspartame