title: Metabolic disturbances and worsening of atherosclerotic lesions in ApoE-/- mice after cola beverages drinking.
abstract: Atherosclerosis 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.
  
  
  
  ApoE-/- 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 (
  
  
  
  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.
  
  
  
  TREATMENT 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.
  
  
  
  Cola 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.
authors.affiliation: Instituto de Investigaciones Cardiológicas Prof, Dr, Alberto C, Taquini (ININCA), Facultad de Medicina, Universidad de Buenos Aires (UBA)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina. mol@fmed.uba.ar
authors.forename: Matilde E
authors.initials: ME
authors.lastname: Otero-Losada
authors.forename: Santiago
authors.initials: S
authors.lastname: Mc Loughlin
authors.forename: Gastón
authors.initials: G
authors.lastname: Rodríguez-Granillo
authors.forename: Angélica
authors.initials: A
authors.lastname: Müller
authors.forename: Graciela
authors.initials: G
authors.lastname: Ottaviano
authors.forename: Marisa
authors.initials: M
authors.lastname: Moriondo
authors.forename: Juan C
authors.initials: JC
authors.lastname: Cutrin
authors.forename: José
authors.initials: J
authors.lastname: Milei
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D001628:Beverages / Q000009:adverse effects*; D030221:Cola; D004326:Drinking / Q000502:physiology*; D005260:Female; D008297:Male; D008659:Metabolic Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D011897:Random Allocation
chemical_list: D001057:Apolipoproteins E
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