Metabolic disturbances and worsening of atherosclerotic lesions in ApoE-/- mice after cola beverages drinking

Abstract

BackgroundAtherosclerosis is a major health burden. Metabolic disorders had been associated with large consumption of soft drinks. The rising incidence of atherosclerosis and metabolic alterations warrants the study of long-term soft drink consumption’ effects on metabolism and atherosclerosis in genetic deficiency of apolipoprotein E which typically develops spontaneous atherosclerosis and metabolic alterations.MethodsApoE-/- mice were randomized in 3 groups accordingly with free access to: water (W), regular cola (C) or light cola (L). After 8 weeks, 50% of the animals in each group were euthanized (Treatment: W8, C8, L8). The remaining mice (all groups) drank water for 8 weeks and were euthanized (Washout: W16, C16, L16). Body weight and food and drink consumption were periodically measured. Blood was collected (biochemistry). At autopsy, transverse aortic sinus sections were serially cut and stained (histomorphometry); livers and kidneys were processed (microscopy). MANOVA (identification of variance factors) was followed by ANOVA and LSD tests (within-factor differences between levels). Conventionally a p< 0.05 was considered significant.ResultsTreatment increased drinking volumes (vs W8: 4 fold C8, p<0.0001; +47% L8, p<0.02). Only C reduced eating amounts (–54%, p<0.05 vs W8). I). Compared with W8: C8 developed hyperglycemia (+43%, p<0.03) and increased non-HDL cholesterol (+54%, p<0.05); L8 showed decreased glycemia (–15%, p<0.05 vs W8) and increased creatinine (2.5 fold, p<0.04), urea (+74, p<0.03) and aspartate-aminotransferase (2.8 fold, p<0.05). Hypercreatininemia was observed in L16 (2.7 fold vs W16, p<0.05). Hypertriglyceridemia (+91%, p<0.008) and hyperuremia (+68%, p<0.03) developed over time of study (age). II). Treatment caused plaque area increase (vs W8: 28% C8, p<0.02 and 50% L8, p<0.01; vs W16: 43% C16, p<0.05 and 68% L16, p<0.02) and stenosis (vs W8: 38% C8, p<0.04 and 57% L8, p<0.01; vs W16: 71% C16, p<0.01 and 46% L16, p<0.04). Age also caused plaque area increase (56%, p<0.04). Treatment- and age-effects on plaque enlargement were additive.ConclusionCola beverages caused atherosclerotic lesions’ enlargement with metabolic (C) or non metabolic disturbances (L). ApoE-/- mice were particularly sensitive to L treatment. These findings may likely relate to caramel colorant and non-nutritive sweeteners in cola drinks and have potential implications in particularly sensitive individuals.

Non-caloric artificial sweeteners and the microbiome: findings and challenges

“…27 In addition to weight gain, both saccharin and aspartame have been associated with impaired glucose homeostasis in mice, 24,28,29 and aspartame was also shown to induce hyperinsulinemia, 25 impaired insulin tolerance 24,28 and worsened atherosclerosis in genetically-susceptible (ApoE ¡/¡ ) mice. 30,31 In contrast, Flatt and colleagues described anti-hyperglycemic and antihyperinsulinemic effects for saccharin in genetically obese (ob/ob) mice, coupled with attenuation of weight gain. 32 In fact, beneficial effects of NAS were at times described to co-occur with detrimental ones in some studies.…”

Rate of Atherosclerosis Progression in ApoE−/− Mice Long After Discontinuation of Cola Beverage Drinking

“…Previously we reported paradoxical worsening of atherosclerosisat the end of cola beveragesdrinking-treatment [10]. However interpretation of these findings could be questioned considering that determinations had been performed at a single time point immediately after drinking-treatment cessation and the recovery period might have been insufficient to observereversal of damage if any.…”

“…Hypertension, hyperglycemia, increased body weight, dyslipidemia and echocardiographic alterations were observed while pathology findings were scarce, related to aging rather than treatment [8], [9]. Recently we observed that ApoE −/− C57BL/6J mice exhibited a particular sensitivity to the effects of cola beverage drinking [10]. Arterial pathology was induced bysucrose-sweetened cola (C) drinking in association with hyperglycemia [10].…”

“…Recently we observed that ApoE −/− C57BL/6J mice exhibited a particular sensitivity to the effects of cola beverage drinking [10]. Arterial pathology was induced bysucrose-sweetened cola (C) drinking in association with hyperglycemia [10]. Unexpectedly artificially-sweetened ‘light’ cola(L) drinking induced non-metabolic changes compared with water drinking ApoE −/− mice [10].…”

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

“…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].…”